2020 |
Milocco, Alessio; Scuor, Nicola; Lughi, Vanni; Lamberti, Gaetano; Barba, Anna Angela; Divittorio, Rosario; Grassi, Gabriele; Perkan, Andrea; Grassi, Mario; Abrami, Michela Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty Journal Article Journal of Applied Polymer Science, 137 (25), pp. 10, 2020. Abstract | Links | BibTeX | Tags: alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis @article{Milocco2020, title = {Thermal gelation modeling of a pluronic-alginate blend following coronary angioplasty }, author = {Alessio Milocco and Nicola Scuor and Vanni Lughi and Gaetano Lamberti and Anna Angela Barba and Rosario Divittorio and Gabriele Grassi and Andrea Perkan and Mario Grassi and Michela Abrami}, url = {https://onlinelibrary.wiley.com/doi/epdf/10.1002/app.48539}, doi = {10.1002/app.48539}, year = {2020}, date = {2020-07-05}, journal = {Journal of Applied Polymer Science}, volume = {137}, number = {25}, pages = {10}, abstract = {To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. }, keywords = {alginate-pluronic, coronary angioplasty, Mathematical modeling, restenosis}, pubstate = {published}, tppubtype = {article} } To overcome the complications connected to the treatment of coronary atherosclerosis by means of percutaneous transluminal angioplasty followed by stent implantation, the in situ release of antiproliferative nucleic acid based drugs (NABD) seems a promising approach. For their fragile nature, NABD cannot be released from drug eluting stents but they need to be embedded in a soft gel coating the coronary wall (endoluminal gel paving). This article deals with the thermal fate, once in the catheter, of a polymer blend composed by pluronic, giving rise to a soft gel in water upon temperature rise, and alginate, a natural polysaccharide giving origin to a strong gel in the presence of divalent cations. Simulations reveal that while the formation of a pregel is rapidly achieved, the formation of a mature gel takes a much longer time with respect to the residence time of the polymer blend inside the catheter. |
Bochicchio, Sabrina; Dalmoro, Annalisa; Simone, Veronica De; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems Journal Article Cosmetics, 7 (22), pp. 13, 2020. Abstract | Links | BibTeX | Tags: antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery @article{Bochicchio2020, title = {Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems}, author = {Sabrina Bochicchio and Annalisa Dalmoro and Veronica De Simone and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba}, editor = {MDPI}, url = {https://www.mdpi.com/2079-9284/7/2/22/pdf}, doi = {10.3390/cosmetics7020022}, year = {2020}, date = {2020-04-03}, journal = {Cosmetics}, volume = {7}, number = {22}, pages = {13}, abstract = {Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84\textendash145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. }, keywords = {antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery}, pubstate = {published}, tppubtype = {article} } Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84–145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. |
Barba, Anna Angela; Dalmoro, Annalisa; Bochicchio, Sabrina; Simone, Veronica De; Caccavo, Diego; Iannone, Marco; Lamberti, Gaetano Engineering approaches for drug delivery systems production and characterization Journal Article International Journal of Pharmaceutics, 2020. Abstract | Links | BibTeX | Tags: drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors @article{Barba2020, title = {Engineering approaches for drug delivery systems production and characterization}, author = {Anna Angela Barba and Annalisa Dalmoro and Sabrina Bochicchio and Veronica De Simone and Diego Caccavo and Marco Iannone and Gaetano Lamberti}, editor = {Elsevier B.V.}, url = {https://www.sciencedirect.com/science/article/pii/S0378517320302519}, doi = {10.1016/j.ijpharm.2020.119267}, year = {2020}, date = {2020-03-31}, journal = {International Journal of Pharmaceutics}, abstract = {To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs). In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.}, keywords = {drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors}, pubstate = {published}, tppubtype = {article} } To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs). In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported. |
Lamberti, Gaetano; Barba, Anna Angela Drug Delivery of siRNA Therapeutics Journal Article Pharmaceutics, 12(2) (178), 2020. Links | BibTeX | Tags: aptamers, Drug Delivery Systems, gene therapy, liposomes, nanoparticles, polycations, siRNA @article{Lamberti2020, title = {Drug Delivery of siRNA Therapeutics}, author = {Gaetano Lamberti and Anna Angela Barba}, url = {https://www.mdpi.com/1999-4923/12/2/178/pdf}, doi = {10.3390/pharmaceutics12020178}, year = {2020}, date = {2020-02-20}, journal = {Pharmaceutics}, volume = {12(2)}, number = {178}, keywords = {aptamers, Drug Delivery Systems, gene therapy, liposomes, nanoparticles, polycations, siRNA}, pubstate = {published}, tppubtype = {article} } |
Cascone, Sara; Lamberti, Gaetano Hydrogel-based commercial products for biomedical applications: a review Journal Article International Journal of Pharmaceutics, 573 (118803), pp. 1-19, 2020. Abstract | Links | BibTeX | Tags: biomedical applications, commercial products, drug delivery, Hydrogels @article{Cascone2019, title = {Hydrogel-based commercial products for biomedical applications: a review}, author = {Sara Cascone and Gaetano Lamberti}, url = {https://www.sciencedirect.com/science/article/pii/S0378517319308488?via%3Dihub}, doi = {10.1016/j.ijpharm.2019.118803}, year = {2020}, date = {2020-01-05}, journal = {International Journal of Pharmaceutics}, volume = {573}, number = {118803}, pages = {1-19}, abstract = {Hydrogels are hydrophilic polymer networks, able to absorb large amount of water, increasing their volume and showing a plethora of different material behaviors. Since their first practical application, dating from sixties of last century, they have been employed in several fields of biomedical sciences. After more than half a century of industrial uses, nowadays a lot of hydrogels are currently on the market for different purposes, and offering a wide spectra of features. In this review, even if it is virtually impossible to list all the commercial products based on hydrogels for biomedical applications, an extensive analysis of those materials that have reached the market has been carried out. The hydrogel-based materials used for drug delivery, wound dressing, tissue engineering, the building of contact lens, and hygiene products are enlisted and briefly described. A detailed snapshot of the set of these products that have reached the commercial maturity has been then obtained and presented. For each class of application, the basics of requirements are described, and then the materials are listed and classified on the basis of their chemical nature. For each product the commercial name, the producer, the chemical nature and the main characteristics are reported.}, keywords = {biomedical applications, commercial products, drug delivery, Hydrogels}, pubstate = {published}, tppubtype = {article} } Hydrogels are hydrophilic polymer networks, able to absorb large amount of water, increasing their volume and showing a plethora of different material behaviors. Since their first practical application, dating from sixties of last century, they have been employed in several fields of biomedical sciences. After more than half a century of industrial uses, nowadays a lot of hydrogels are currently on the market for different purposes, and offering a wide spectra of features. In this review, even if it is virtually impossible to list all the commercial products based on hydrogels for biomedical applications, an extensive analysis of those materials that have reached the market has been carried out. The hydrogel-based materials used for drug delivery, wound dressing, tissue engineering, the building of contact lens, and hygiene products are enlisted and briefly described. A detailed snapshot of the set of these products that have reached the commercial maturity has been then obtained and presented. For each class of application, the basics of requirements are described, and then the materials are listed and classified on the basis of their chemical nature. For each product the commercial name, the producer, the chemical nature and the main characteristics are reported. |
2019 |
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano Polymeric and lipid-based systems for controlled drug release: an engineering point of view Book Chapter Grumezescu, Alexandru Mihai (Ed.): Chapter 10, pp. 267-304, Elsevier, 2019, ISBN: 978-0-12-816505-8. Abstract | Links | BibTeX | Tags: characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes @inbook{Barba2019c, title = {Polymeric and lipid-based systems for controlled drug release: an engineering point of view}, author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Diego Caccavo and Sara Cascone and Gaetano Lamberti}, editor = {Alexandru Mihai Grumezescu}, url = {https://www.sciencedirect.com/science/article/pii/B9780128165058000138?via%3Dihub#kys0010}, doi = {10.1016/B978-0-12-816505-8.00013-8}, isbn = {978-0-12-816505-8}, year = {2019}, date = {2019-12-02}, pages = {267-304}, publisher = {Elsevier}, chapter = {10}, abstract = {Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view. The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared.}, keywords = {characterization techniques, controlled release, lipid nanoparticles, Mathematical modeling, Polymer nanoparticles, production processes}, pubstate = {published}, tppubtype = {inbook} } Aim of this chapter is to review the most common techniques to produce and to characterize systems for controlled drug release, giving particular emphasis to the fundamentals of the production processes and to the possibility to describe mathematically the phenomena involved in drug release, that is, looking at the processes from an engineering point of view. The most commonly used materials are briefly reviewed, both the polymeric materials (preformed and ad-hoc synthetized, natural, and synthetic) as well as the lipid materials. Then, the drug delivery systems’ preparation processes are presented and discussed. Particular focus is given to the preparation of micro- and nanoparticles based on preformed polymers, and to preparation processes for liposomes. Advanced characterization techniques for novel and conventional drug delivery systems are then presented. Last but not least, the most modern modeling approaches to describe the drug release from these drug delivery systems are reported and compared. |
Barba, Anna Angela; Bochicchio, Sabrina; Bertoncin, Paolo; Lamberti, Gaetano; Dalmoro, Annalisa Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches Journal Article Coatings, 9 (491), pp. 1-15, 2019. Abstract | Links | BibTeX | Tags: Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique @article{Barba2019b, title = {Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches }, author = {Anna Angela Barba and Sabrina Bochicchio and Paolo Bertoncin and Gaetano Lamberti and Annalisa Dalmoro}, url = {https://www.mdpi.com/2079-6412/9/8/491/htm}, doi = {10.3390/coatings9080491}, year = {2019}, date = {2019-08-02}, journal = {Coatings}, volume = {9}, number = {491}, pages = {1-15}, abstract = {Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability.}, keywords = {Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique}, pubstate = {published}, tppubtype = {article} } Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability. |
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Lamberti, Gaetano Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications Journal Article Pharmaceutics, 11 (360), 2019. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Barba2019, title = {Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications}, author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti}, url = {https://www.mdpi.com/1999-4923/11/8/360}, doi = {10.3390/pharmaceutics11080360}, year = {2019}, date = {2019-07-24}, journal = {Pharmaceutics}, volume = {11}, number = {360}, abstract = {In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs |
Dalmoro, Annalisa; Bochicchio, Sabrina; Lamberti, Gaetano; Bertoncin, Paolo; Janssens, Barbara; Barba, Anna Angela Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology Journal Article RSC Advances, 9 , pp. 19800-19812, 2019. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, Micro and Nano Vectors @article{Dalmoro2019, title = {Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology }, author = {Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Paolo Bertoncin and Barbara Janssens and Anna Angela Barba}, url = {https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k}, doi = {10.1039/C9RA03022K}, year = {2019}, date = {2019-06-25}, journal = {RSC Advances}, volume = {9}, pages = {19800-19812}, abstract = {Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer\textendashlipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.}, keywords = {Drug Delivery Systems, Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer–lipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications. |
Caccavo, Diego An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems Journal Article International Journal of Pharmaceutics, 560 , pp. 175-190, 2019. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2019, title = {An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems}, author = {Diego Caccavo}, url = {https://www.sciencedirect.com/science/article/pii/S0378517319301188?via%3Dihub}, doi = {10.1016/j.ijpharm.2019.01.076}, year = {2019}, date = {2019-02-11}, journal = {International Journal of Pharmaceutics}, volume = {560}, pages = {175-190}, abstract = {Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models. |
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela Effect of binder and load solubility properties on HPMC granules produced by wet granulation process Journal Article Journal of Drug Delivery Science and Technology, 49 , pp. 513-520, 2019. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Simone}2019, title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process}, author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043}, doi = {10.1016/j.jddst.2018.12.030}, year = {2019}, date = {2019-02-01}, journal = {Journal of Drug Delivery Science and Technology}, volume = {49}, pages = {513-520}, abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively. |
2018 |
De Simone, Veronica ; Caccavo, Diego; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela Wet-granulation process: phenomenological analysis and process parameters optimization Journal Article Powder Technology, 340 , pp. 411-419, 2018. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Simone}2018b, title = {Wet-granulation process: phenomenological analysis and process parameters optimization}, author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800}, doi = {10.1016/j.powtec.2018.09.053}, year = {2018}, date = {2018-12-01}, journal = {Powder Technology}, volume = {340}, pages = {411-419}, abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000–10,000 μm) as the main variable of interest. |
De Simone, Veronica ; Caccavo, Diego; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters Book Chapter Kyzas, George (Ed.): Chapter 5, IntechOpen, 2018, ISBN: 978-1-78984-308-8. Abstract | Links | BibTeX | Tags: Granulation, HPMC, Mathematical modeling @inbook{Simone}2018c, title = {Inside the Phenomenological Aspects of Wet Granulation: Role of Process Parameters}, author = {Veronica {De Simone} and Diego Caccavo and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba}, editor = {George Kyzas}, url = {https://www.intechopen.com/books/granularity-in-materials-science/inside-the-phenomenological-aspects-of-wet-granulation-role-of-process-parameters}, doi = {10.5772/intechopen.79840}, isbn = {978-1-78984-308-8}, year = {2018}, date = {2018-10-24}, publisher = {IntechOpen}, chapter = {5}, abstract = {Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed.}, keywords = {Granulation, HPMC, Mathematical modeling}, pubstate = {published}, tppubtype = {inbook} } Granulation is a size-enlargement process by which small particles are bonded, by means of various techniques, in coherent and stable masses (granules), in which the original particles are still identifiable. In wet granulation processes, the powder particles are aggregated through the use of a liquid phase called binder. The main purposes of size-enlargement process of a powder or mixture of powders are to improve technological properties and/or to realize suitable forms of commercial products. A modern and rational approach in the production of granular structures with tailored features (in terms of size and size distribution, flowability, mechanical and release properties, etc.) requires a deep understanding of phenomena involved during granules formation. By this knowledge, suitable predictive tools can be developed with the aim to choose right process conditions to be used in developing new formulations by avoiding or reducing costs for new tests. In this chapter, after introductive notes on granulation process, the phenomenological aspects involved in the formation of the granules with respect to the main process parameters are presented by experimental demonstration. Possible mathematical approaches in the granulation process description are also presented and the one involving the population mass balances equations is detailed. |
Bochicchio, Sabrina; Dalmoro, Annalisa; Bertoncin, Paolo; Lamberti, Gaetano; Moustafine, Rouslan I; Barba, Anna Angela Design and production of hybrid nanoparticles with polymeric-lipid shell–core structures: conventional and next-generation approaches Journal Article RSC Advances, 8 , pp. 34614–34624, 2018. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Bochicchio2018, title = {Design and production of hybrid nanoparticles with polymeric-lipid shell\textendashcore structures: conventional and next-generation approaches}, author = {Sabrina Bochicchio and Annalisa Dalmoro and Paolo Bertoncin and Gaetano Lamberti and Rouslan I. Moustafine and Anna Angela Barba }, url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract}, doi = {10.1039/c8ra07069e}, year = {2018}, date = {2018-09-27}, journal = {RSC Advances}, volume = {8}, pages = {34614\textendash34624}, abstract = {Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the natural biocompatible polymer chitosan to achieve stable shell\textendashcore nanostructures. Covered nanoliposomes were produced using an innovative continuous method based on microfluidic principles. The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties, size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method were compared with those of the conventional dropwise method and the obtained products. The proposed simil-microfluidic method led to the production of stable and completely chitosan-covered liposomes with a shell\textendashcore nanostructure that avoided the disadvantages inherent in the conventional method (which are time-consuming and/or require bulky and more expensive equipment).}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the natural biocompatible polymer chitosan to achieve stable shell–core nanostructures. Covered nanoliposomes were produced using an innovative continuous method based on microfluidic principles. The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties, size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method were compared with those of the conventional dropwise method and the obtained products. The proposed simil-microfluidic method led to the production of stable and completely chitosan-covered liposomes with a shell–core nanostructure that avoided the disadvantages inherent in the conventional method (which are time-consuming and/or require bulky and more expensive equipment). |
Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems Journal Article European Journal of Pharmaceutical Sciences, 121 , pp. 16-28, 2018. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Dalmoro2018b, title = {Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems}, author = {Annalisa Dalmoro and Sabrina Bochicchio and Shamil F. Nasibullin and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine}, url = {https://www.sciencedirect.com/science/article/pii/S0928098718302331}, doi = {10.1016/j.ejps.2018.05.014}, year = {2018}, date = {2018-08-30}, journal = {European Journal of Pharmaceutical Sciences}, volume = {121}, pages = {16-28}, abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity. Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods. The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin. Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing. |
Caccavo, Diego; Vietri, Antonella; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Modeling the mechanics and the transport phenomena in hydrogels Book Chapter Manca, Davide (Ed.): Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications, Chapter 12, 2018. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inbook{Caccavo2018b, title = {Modeling the mechanics and the transport phenomena in hydrogels}, author = {Diego Caccavo and Antonella Vietri and Gaetano Lamberti and Anna Angela Barba and Anette Larsson }, editor = {Davide Manca}, url = {https://www.sciencedirect.com/science/article/pii/B978044463964600012X}, doi = {10.1016/B978-0-444-63964-6.00012-X}, year = {2018}, date = {2018-07-18}, booktitle = {Quantitative Systems Pharmacology: Models and Model-Based Systems with Applications}, chapter = {12}, abstract = {Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as\textemdashin principle\textemdashany other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters).}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inbook} } Hydrogels are polymeric materials widely used in pharmaceutical and biomedical applications. Their uses can be improved by modeling their behavior, in particular the mechanical phenomena and the transport phenomena. The scope of this chapter is to propose a model, simple enough and with a limited number of parameters to be determined, able to capture the full behavior of a swelling hydrogel, with the aim of describing the drug release process as well as—in principle—any other application of hydrogels. The model was derived recalling the basics of the continuum mechanics, the possible approaches to estimate the Helmholtz free energy, and then writing the transport and constitutive equations for a poroelastic material, and for a more realistic poroviscoelastic material (by adding the standard linear solid model as the rheological model). A full extension to multicomponent systems, to describe the drug release phenomenon, is proposed along with a sensitivity analysis (free-swelling simulation by changing the model parameters). |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour Journal Article Chemical Society Reviews, 47 (7), pp. 2357-2373, 2018, ISSN: 0306-0012. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2018, title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract}, doi = {10.1039/C7CS00638A}, issn = {0306-0012}, year = {2018}, date = {2018-04-07}, journal = {Chemical Society Reviews}, volume = {47}, number = {7}, pages = {2357-2373}, abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure–property relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented. |
Dalmoro, Annalisa; Naddeo, Carlo; Caputo, Silvestro; Lamberti, Gaetano; Guadagno, Liberata; D'Amore, Matteo; Barba, Anna Angela On the relevance of thermophysic characterizations in microwave treatments of legumes Journal Article Food & Function, 9 (3), pp. 1816-1828, 2018, ISSN: 2042-650X. Abstract | Links | BibTeX | Tags: legumes, microwave, Tecnagri, thermophysic @article{Dalmoro2018, title = {On the relevance of thermophysic characterizations in microwave treatments of legumes}, author = {Annalisa Dalmoro and Carlo Naddeo and Silvestro Caputo and Gaetano Lamberti and Liberata Guadagno and Matteo D'Amore and Anna Angela Barba}, url = {http://pubs.rsc.org/en/Content/ArticleLanding/2018/FO/C7FO01488K}, doi = {10.1039/C7FO01488K}, issn = {2042-650X}, year = {2018}, date = {2018-03-01}, journal = {Food & Function}, volume = {9}, number = {3}, pages = {1816-1828}, abstract = {This study is focused on the characterization of thermal behavior and physical properties of most consumed legumes in daily diet such as beans, lentils and chickpeas. Because of a lack of knowledge in literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable to inactivate the infesting fauna, and one simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenols composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also performed. Examined legumes thermal properties were found comparable for all samples. Similarly, no significative differences in antinutritional factors, polyphenols and tannins, content among all samples were detected. Under structural point of view, samples exposed to high temperatures have been shown a texture degradation and in turn, losses of mineral nutrient during soaking processes. Moreover, their germinative capability was drastically reduced. These latter results highlighted how is important to correctly perform radiative microwave process in order to both assure an effective and safe disinfestation and avoid nutritional values losses and physical properties worsening.}, keywords = {legumes, microwave, Tecnagri, thermophysic}, pubstate = {published}, tppubtype = {article} } This study is focused on the characterization of thermal behavior and physical properties of most consumed legumes in daily diet such as beans, lentils and chickpeas. Because of a lack of knowledge in literature about the effect of microwave treatments on legumes, characterization protocols have been applied before and after subjecting them to microwave irradiation suitable for pest disinfestation. The effects of two different radiative treatments, one suitable to inactivate the infesting fauna, and one simulating uncontrolled treatments, characterized by very high temperatures, were tested. The impacts of microwave treatments on legumes, in terms of thermal behavior, germination capability, tannin and total polyphenols composition and other physical properties (water uptake capability, texture change, mineral losses), after typical soaking cooking processes, are also performed. Examined legumes thermal properties were found comparable for all samples. Similarly, no significative differences in antinutritional factors, polyphenols and tannins, content among all samples were detected. Under structural point of view, samples exposed to high temperatures have been shown a texture degradation and in turn, losses of mineral nutrient during soaking processes. Moreover, their germinative capability was drastically reduced. These latter results highlighted how is important to correctly perform radiative microwave process in order to both assure an effective and safe disinfestation and avoid nutritional values losses and physical properties worsening. |
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; Caccavo, Diego; D'Amore, Matteo; Barba, Anna Angela HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties Journal Article Carbohydrate Polymers, 181 , pp. 939-947, 2018. Abstract | Links | BibTeX | Tags: Granulation @article{{DeSimone}2018, title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties}, author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba }, url = {http://www.sciencedirect.com/science/article/pii/S0144861717313425}, doi = {10.1016/j.carbpol.2017.11.056}, year = {2018}, date = {2018-02-01}, journal = {Carbohydrate Polymers}, volume = {181}, pages = {939-947}, abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.}, keywords = {Granulation}, pubstate = {published}, tppubtype = {article} } Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45–2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45–2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation. |
Cascone, Sara; Lamberti, Gaetano; Piazza, Ornella; Abbiati, Roberto Andrea; Manca, Davide A physiologically-based model to predict individual pharmacokinetics and pharmacodynamics of remifentanil Journal Article European Journal of Pharmaceutical Sciences, 111 , pp. 20-28, 2018, ISSN: 0928-0987. Abstract | Links | BibTeX | Tags: Modeling, Pharmacokinetics @article{Cascone2018, title = {A physiologically-based model to predict individual pharmacokinetics and pharmacodynamics of remifentanil}, author = {Sara Cascone and Gaetano Lamberti and Ornella Piazza and Roberto Andrea Abbiati and Davide Manca}, url = {http://www.sciencedirect.com/science/article/pii/S0928098717305201}, doi = {10.1016/j.ejps.2017.09.028}, issn = {0928-0987}, year = {2018}, date = {2018-01-01}, journal = {European Journal of Pharmaceutical Sciences}, volume = {111}, pages = {20-28}, abstract = {Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also by a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology. The aims of this work are to propose and validate a physiologically based pharmacokinetic model capable to predict both the pharmacokinetics and pharmacodynamics of remifentanil, and to take into account the inter-individual differences among the patients (such as height and body mass). The blood concentration of remifentanil has been successfully simulated and compared with experimental literature data. The pharmacodynamics, in terms of effect of remifentanil on minute ventilation and electroencephalogram, has been implemented in this model. Moreover, the remifentanil concentration in various organs and tissues is predicted, which is a significant improvement with respect to the traditional compartmental models. The availability of the model makes possible the prediction of the effects of remifentanil administration, also accounting for individual parameters.}, keywords = {Modeling, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } Remifentanil based anesthesia is nowadays spread worldwide. This drug is characterized by a rapid onset of the analgesic effects, but also by a rapid onset of the side effects. For this reason, the knowledge of the remifentanil concentration in the human body is a key topic in anesthesiology. The aims of this work are to propose and validate a physiologically based pharmacokinetic model capable to predict both the pharmacokinetics and pharmacodynamics of remifentanil, and to take into account the inter-individual differences among the patients (such as height and body mass). The blood concentration of remifentanil has been successfully simulated and compared with experimental literature data. The pharmacodynamics, in terms of effect of remifentanil on minute ventilation and electroencephalogram, has been implemented in this model. Moreover, the remifentanil concentration in various organs and tissues is predicted, which is a significant improvement with respect to the traditional compartmental models. The availability of the model makes possible the prediction of the effects of remifentanil administration, also accounting for individual parameters. |
2017 |
Caccavo, Diego; Cascone, Sara; Apicella, Pietro; Lamberti, Gaetano; Barba, Anna Angela HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture Journal Article Chemical Engineering Communications, 204 (12), pp. 1333-1340, 2017, ISSN: 0098-6445. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Caccavo2017b, title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture}, author = {Diego Caccavo and Sara Cascone and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398}, doi = {10.1080/00986445.2017.1362398 }, issn = {0098-6445}, year = {2017}, date = {2017-12-01}, journal = {Chemical Engineering Communications}, volume = {204}, number = {12}, pages = {1333-1340}, abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices. |
Bochicchio, Sabrina; Sala, Marina; Spensiero, Antonia; Scala, Maria Carmina; Gomez-Monterrey, Isabel; Lamberti, Gaetano; Barba, Anna Angela On the design of tailored liposomes for KRX29 peptide delivery Journal Article New Journal of Chemistry, 41 (19), pp. 11280-11290, 2017, ISSN: 1144-0546. Abstract | Links | BibTeX | Tags: liposome, peptide @article{Bochicchio2017b, title = {On the design of tailored liposomes for KRX29 peptide delivery }, author = {Sabrina Bochicchio and Marina Sala and Antonia Spensiero and Maria Carmina Scala and Isabel Gomez-Monterrey and Gaetano Lamberti and Anna Angela Barba }, url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ03115G}, doi = { 10.1039/C7NJ03115G}, issn = {1144-0546}, year = {2017}, date = {2017-12-01}, journal = {New Journal of Chemistry}, volume = {41}, number = {19}, pages = {11280-11290}, abstract = {The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 \textendash 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction.}, keywords = {liposome, peptide}, pubstate = {published}, tppubtype = {article} } The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 – 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction. |
Caccavo, Diego; Barba, Anna Angela; D'Amore, Matteo; De Piano, Raffaella ; Lamberti, Gaetano; Rossi, Alessandra; Colombo, Paolo Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix® Journal Article European Journal of Pharmaceutics and Biopharmaceutics, 121 , pp. 24-31, 2017, ISSN: 0939-6411. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®}, author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo}, url = {http://www.sciencedirect.com/science/article/pii/S0939641117308366}, doi = {10.1016/j.ejpb.2017.08.016}, issn = {0939-6411}, year = {2017}, date = {2017-12-01}, journal = {European Journal of Pharmaceutics and Biopharmaceutics}, volume = {121}, pages = {24-31}, abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped. |
Bochicchio, Sabrina; Lamberti, Gaetano; Barba, Anna Angela Phenomenological and Formulation Aspects in Tailored Nanoliposome Production Book Chapter Liposomes, Chapter 2, IntechOpen, 2017. Abstract | Links | BibTeX | Tags: cell‐mimetic system, gene therapy, liposome, nanoliposomes delivery systems, nutraceuticals, personalized carriers, simil‐microfluidic approach, ultrasonic size reduction @inbook{Bochicchio2017d, title = {Phenomenological and Formulation Aspects in Tailored Nanoliposome Production}, author = {Sabrina Bochicchio and Gaetano Lamberti and Anna Angela Barba}, url = {https://www.intechopen.com/books/liposomes/phenomenological-and-formulation-aspects-in-tailored-nanoliposome-production}, doi = {10.5772/intechopen.68157}, year = {2017}, date = {2017-10-25}, booktitle = {Liposomes}, publisher = {IntechOpen}, chapter = {2}, abstract = {Liposomes as cell‐mimetic system have attracted wide attention of researchers in various branches of the drug delivery topic as they can be highly functionalized and personalized, thus solving the major drawbacks of bioactive molecules linked to their low stability, limited membrane permeability, short half‐life and low bioavailability. The development of sustainable processes able to produce ad hoc liposomes in a rapid manner through the use of not‐laboured techniques, avoiding drastic conditions, is of great relevance for the industrial sector. In this chapter, two novel liposome production processes, the ultrasound‐assisted thin‐film hydration and the simil‐microfluidic techniques sharing the same size reduction/homogenization preparative step, are presented. The phenomenological aspects involved in vectors constitution through the duty cycle sonication process (bilayer rupture/vesicles formation mechanisms) and through the simil‐microfluidic approach (intubated flows interdiffusion mechanisms) are described. Finally, two applications as case histories involving the use of the developed techniques for relevant classes of active molecule delivery are described. In particular, a pharmaceutical application concerns the encapsulation of short‐interfering RNA (siRNA) molecule, used for gene therapy, inside cationic nanoliposomes, and a nutraceutical application consists in the production of ferrous sulphate anionic liposomal formulations with improved features compared to those already present on the market.}, keywords = {cell‐mimetic system, gene therapy, liposome, nanoliposomes delivery systems, nutraceuticals, personalized carriers, simil‐microfluidic approach, ultrasonic size reduction}, pubstate = {published}, tppubtype = {inbook} } Liposomes as cell‐mimetic system have attracted wide attention of researchers in various branches of the drug delivery topic as they can be highly functionalized and personalized, thus solving the major drawbacks of bioactive molecules linked to their low stability, limited membrane permeability, short half‐life and low bioavailability. The development of sustainable processes able to produce ad hoc liposomes in a rapid manner through the use of not‐laboured techniques, avoiding drastic conditions, is of great relevance for the industrial sector. In this chapter, two novel liposome production processes, the ultrasound‐assisted thin‐film hydration and the simil‐microfluidic techniques sharing the same size reduction/homogenization preparative step, are presented. The phenomenological aspects involved in vectors constitution through the duty cycle sonication process (bilayer rupture/vesicles formation mechanisms) and through the simil‐microfluidic approach (intubated flows interdiffusion mechanisms) are described. Finally, two applications as case histories involving the use of the developed techniques for relevant classes of active molecule delivery are described. In particular, a pharmaceutical application concerns the encapsulation of short‐interfering RNA (siRNA) molecule, used for gene therapy, inside cationic nanoliposomes, and a nutraceutical application consists in the production of ferrous sulphate anionic liposomal formulations with improved features compared to those already present on the market. |
Cascone, Sara; De Santis, Felice ; Lamberti, Gaetano Mimicking the contractions of a human stomach and their effect on pharmaceuticals Journal Article Journal of Drug Delivery Science and Technology, 41 , pp. 454-461, 2017, ISSN: 1773-2247. Abstract | Links | BibTeX | Tags: Pharmacokinetics @article{Cascone2017b, title = {Mimicking the contractions of a human stomach and their effect on pharmaceuticals}, author = {Sara Cascone and Felice {De Santis} and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S1773224717305907}, doi = {10.1016/j.jddst.2017.09.008}, issn = {1773-2247}, year = {2017}, date = {2017-10-01}, journal = {Journal of Drug Delivery Science and Technology}, volume = {41}, pages = {454-461}, abstract = {The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.}, keywords = {Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body. |
Cascone, Sara Modeling and comparison of release profiles: Effect of the dissolution method Journal Article European Journal of Pharmaceutical Sciences, 106 , pp. 352-361, 2017, ISSN: 0928-0987. Abstract | Links | BibTeX | Tags: drug release, In silico, In vitro, Pharmacokinetics @article{Cascone2017, title = {Modeling and comparison of release profiles: Effect of the dissolution method}, author = {Sara Cascone}, url = {http://www.sciencedirect.com/science/article/pii/S092809871730355X}, doi = {10.1016/j.ejps.2017.06.021}, issn = {0928-0987}, year = {2017}, date = {2017-08-30}, journal = {European Journal of Pharmaceutical Sciences}, volume = {106}, pages = {352-361}, abstract = {During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach. Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified.}, keywords = {drug release, In silico, In vitro, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } During the last decades, the study of the in vitro dissolution of pharmaceuticals has been strongly encouraged by the FDA in order to determine its relationship with the in vivo bioavailability of a drug. In this work immediate and extended release formulations containing diclofenac, a BCS class II drug, were studied using different dissolution methods. The release profiles obtained in USP Apparatus II and USP Apparatus IV were evaluated and compared to determine the effect of the fluid dynamic conditions on the release. The influence of the mixing conditions (i.e. the paddle rotation speed in USP Apparatus II or the inlet flow rate in USP Apparatus IV) on the drug release were evaluated, finding that, for the extended release formulations, they do not affect significantly the release profile. An in vitro device simulating the peristaltic contractions of the stomach during the digestion was used to simulate fluid dynamics closer to the real physiology. The tablets were found to behave in a completely different way if tested in the artificial stomach. Both model-independent and model-dependent approaches were used to compare and fit the dissolution profiles, respectively. Fit factors were used as indicators of similarity of two dissolution profiles; model equations (such as zero-order, first-order, or Korsmeyer-Peppas equations) were used to fit the experimental data. With the identification of the best fitting model by the use of correlation factors and Akaike Information Criterion, the transport phenomena that determine the behavior of each formulation were identified. |
Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Abrahmsén-Alami, Susanna; Viridén, Anna; Larsson, Anette Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study Journal Article International Journal of Pharmaceutics, 528 (1-2), pp. 705-713, 2017, ISSN: 0378-5173. Abstract | Links | BibTeX | Tags: Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling @article{Larsson2017, title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study}, author = {Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Susanna Abrahms\'{e}n-Alami and Anna Virid\'{e}n and Anette Larsson}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317305720}, doi = {10.1016/j.ijpharm.2017.06.064}, issn = {0378-5173}, year = {2017}, date = {2017-08-07}, journal = {International Journal of Pharmaceutics}, volume = {528}, number = {1-2}, pages = {705-713}, abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. }, keywords = {Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling}, pubstate = {published}, tppubtype = {article} } The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. |
Bochicchio, Sabrina; Dalmoro, Annalisa; Recupido, Federica; Lamberti, Gaetano; Barba, Anna Angela Nanoliposomes Production by a Protocol Based on a Simil-Microfluidic Approach Book Chapter Piotto, Stefano; Rossi, Federico; Concilio, Simona; Reverchon, Ernesto; Cattaneo, Giuseppe (Ed.): Chapter 1, pp. 3-10, Springer International Publishing AG 2018, 2017, ISBN: 978-3-319-62026-8. Abstract | Links | BibTeX | Tags: liposome @inbook{Bochicchio2017b, title = {Nanoliposomes Production by a Protocol Based on a Simil-Microfluidic Approach}, author = {Sabrina Bochicchio and Annalisa Dalmoro and Federica Recupido and Gaetano Lamberti and Anna Angela Barba}, editor = {Stefano Piotto and Federico Rossi and Simona Concilio and Ernesto Reverchon and Giuseppe Cattaneo}, url = {https://link.springer.com/chapter/10.1007/978-3-319-62027-5_1}, doi = {10.1007/978-3-319-62027-5_1}, isbn = {978-3-319-62026-8}, year = {2017}, date = {2017-08-01}, pages = {3-10}, publisher = {Springer International Publishing AG 2018}, chapter = {1}, series = {Lecture Notes in Bioengineering book}, abstract = {In this work a protocol based on the microfluidic principles has been developed and applied to produce nanoliposomes. The protocol basically consists in the realization of a contact between two flows, lipids/ethanol and water solutions, inside a tubular device where interdiffusion phenomena allow the formation of lipid vesicles. Effects of solutions flow rates and lipids concentrations on size and size distribution have been investigated. Moreover, ultrasonic energy was used to enhance homogenization of the hydroalcoholic final solutions and to promote the vesicles size reduction. By this protocol a massive output has been achieved; increasing the ratio between the water volumetric flow rate to the lipids-ethanol volumetric flow rate the liposomes dimension decreases; at equal flow rates, when the lipids concentration increases also the liposomes size has been observed increasing. }, keywords = {liposome}, pubstate = {published}, tppubtype = {inbook} } In this work a protocol based on the microfluidic principles has been developed and applied to produce nanoliposomes. The protocol basically consists in the realization of a contact between two flows, lipids/ethanol and water solutions, inside a tubular device where interdiffusion phenomena allow the formation of lipid vesicles. Effects of solutions flow rates and lipids concentrations on size and size distribution have been investigated. Moreover, ultrasonic energy was used to enhance homogenization of the hydroalcoholic final solutions and to promote the vesicles size reduction. By this protocol a massive output has been achieved; increasing the ratio between the water volumetric flow rate to the lipids-ethanol volumetric flow rate the liposomes dimension decreases; at equal flow rates, when the lipids concentration increases also the liposomes size has been observed increasing. |
Dalmoro, Annalisa; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides Journal Article Natural Product Communications, 12 (6), pp. 863-866, 2017, ISSN: 1934-578X. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors, microencapsulation, ultrasonic atomization @article{NPC01, title = {Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides}, author = {Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.naturalproduct.us/index.asp http://gruppotpp.unisa.it/wp-content/uploads/2017/06/Dalmoro-et-al-NPC-126-863-866-2017-Abstract-1.pdf}, issn = {1934-578X}, year = {2017}, date = {2017-07-31}, journal = {Natural Product Communications}, volume = {12}, number = {6}, pages = {863-866}, abstract = {This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).}, keywords = {Micro and Nano Vectors, microencapsulation, ultrasonic atomization}, pubstate = {published}, tppubtype = {article} } This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it). |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications Journal Article Natural Product Communications, 12 (6), pp. 867-871, 2017, ISSN: 1934-578X. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling @article{NPC02, title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba}, url = {http://www.naturalproduct.us/index.asp http://gruppotpp.unisa.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf}, issn = {1934-578X}, year = {2017}, date = {2017-07-31}, journal = {Natural Product Communications}, volume = {12}, number = {6}, pages = {867-871}, abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources. In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications. }, keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources. In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications. |
De Simone, Veronica ; Dalmoro, Annalisa; Lamberti, Gaetano; D'Amore, Matteo; Barba, Anna Angela Central Composite Design in HPMC granulation and correlations between product properties and process parameters Journal Article New Journal of Chemistry, 41 (14), pp. 6504-6513, 2017. Abstract | Links | BibTeX | Tags: Granulation, HPMC @article{Simone}2017, title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters}, author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba}, url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract}, doi = {10.1039/C7NJ01280B}, year = {2017}, date = {2017-07-21}, journal = {New Journal of Chemistry}, volume = {41}, number = {14}, pages = {6504-6513}, abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.}, keywords = {Granulation, HPMC}, pubstate = {published}, tppubtype = {article} } Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production. |
Caccavo, Diego; Lamberti, Gaetano PoroViscoElastic model to describe hydrogels' behavior Journal Article Materials Science and Engineering: C, 76 , pp. 102–113, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2017, title = {PoroViscoElastic model to describe hydrogels' behavior}, author = {Diego Caccavo and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0928493116325760}, doi = {10.1016/j.msec.2017.02.155}, year = {2017}, date = {2017-07-01}, journal = {Materials Science and Engineering: C}, volume = {76}, pages = {102\textendash113}, abstract = {Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior. |
Caccavo, Diego; Cascone, Sara; Poto, Serena; Lamberti, Gaetano; Barba, Anna Angela Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests Journal Article Carbohydrate Polymers, 167 , pp. 136–144, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests}, author = {Diego Caccavo and Sara Cascone and Serena Poto and Gaetano Lamberti and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861717302837}, doi = {10.1016/j.carbpol.2017.03.027}, year = {2017}, date = {2017-07-01}, journal = {Carbohydrate Polymers}, volume = {167}, pages = {136\textendash144}, abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. }, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. |
Barba, Anna Angela; Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Chiarappa, Gianluca; Abrami, Michela; Grassi, Gabriele; Grassi, Mario; Tomaiuolo, Giovanna; Guido, Stefano; Brucato, Valerio; Carfì Pavia, Francesco ; Ghersi, Giulio; La Carrubba, Vincenzo ; Abbiati, Roberto Andrea; Manca, Davide Engineering approaches in siRNA delivery Journal Article International Journal of Pharmaceutics, 525 (2), pp. 343–358, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Barba2017, title = {Engineering approaches in siRNA delivery}, author = {Anna Angela Barba and Sara Cascone and Diego Caccavo and Gaetano Lamberti and Gianluca Chiarappa and Michela Abrami and Gabriele Grassi and Mario Grassi and Giovanna Tomaiuolo and Stefano Guido and Valerio Brucato and Francesco {Carf\`{i} Pavia} and Giulio Ghersi and Vincenzo {La Carrubba} and Roberto Andrea Abbiati and Davide Manca}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317301138}, doi = {10.1016/j.ijpharm.2017.02.032}, year = {2017}, date = {2017-06-20}, journal = {International Journal of Pharmaceutics}, volume = {525}, number = {2}, pages = {343\textendash358}, abstract = {siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications. |
Bochicchio, Sabrina; Dapas, Barbara; Russo, Ilaria; Ciacci, Carolina; Piazza, Ornella; De Smedt, Stefan ; Pottie, Eline; Barba, Anna Angela; Grassi, Gabriele In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer Journal Article International Journal of Pharmaceutics, 525 (2), pp. 377–387, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Bochicchio2017, title = {In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer}, author = {Sabrina Bochicchio and Barbara Dapas and Ilaria Russo and Carolina Ciacci and Ornella Piazza and Stefan {De Smedt} and Eline Pottie and Anna Angela Barba and Gabriele Grassi}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317301011}, doi = {10.1016/j.ijpharm.2017.02.020}, year = {2017}, date = {2017-06-20}, journal = {International Journal of Pharmaceutics}, volume = {525}, number = {2}, pages = {377\textendash387}, abstract = {Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour. siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour. siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine. |
Lamberti, Gaetano Delivery of siRNAs Journal Article International Journal of Pharmaceutics, 525 (2), pp. 291–292, 2017. Links | BibTeX | Tags: Micro and Nano Vectors @article{Lamberti2017, title = {Delivery of siRNAs}, author = {Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317304118}, doi = {10.1016/j.ijpharm.2017.05.010}, year = {2017}, date = {2017-06-20}, journal = {International Journal of Pharmaceutics}, volume = {525}, number = {2}, pages = {291\textendash292}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } |
Kazlauske, Jurgita; Cafaro, Maria Margherita; Caccavo, Diego; Marucci, Maria Grazia; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose Journal Article International Journal of Pharmaceutics, 528 (1-2), pp. 345-353, 2017, ISSN: 0378-5173. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization @article{Kazlauske2017, title = {Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose}, author = {Jurgita Kazlauske and Maria Margherita Cafaro and Diego Caccavo and Maria Grazia Marucci and Gaetano Lamberti and Anna Angela Barba and Anette Larsson}, url = {http://www.sciencedirect.com/science/article/pii/S0378517317304970}, doi = {10.1016/j.ijpharm.2017.05.073}, issn = {0378-5173}, year = {2017}, date = {2017-06-17}, journal = {International Journal of Pharmaceutics}, volume = {528}, number = {1-2}, pages = {345-353}, abstract = {The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.}, keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization}, pubstate = {published}, tppubtype = {article} } The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate. |
Caccavo, Diego; Lamberti, Gaetano; Cafaro, Maria Margherita; Barba, Anna Angela; Kazlauske, Jurgita; Larsson, Anette Mathematical modeling of the drug release from an ensemble of coated pellets Journal Article British Journal of Pharmacology, 174 (12), pp. 1797–1809 , 2017, ISBN: 1476-5381. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling @article{Caccavo2017b, title = {Mathematical modeling of the drug release from an ensemble of coated pellets}, author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson}, url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract}, doi = {10.1111/bph.13776}, isbn = {1476-5381}, year = {2017}, date = {2017-04-22}, journal = {British Journal of Pharmacology}, volume = {174}, number = {12}, pages = {1797\textendash1809 }, abstract = {Background and Purpose Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models. Experimental approach In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets. Key Results In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release. Conclusions and Implications The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.}, keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } Background and Purpose Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models. Experimental approach In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets. Key Results In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release. Conclusions and Implications The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool. |
Dalmoro, Annalisa; Sitenkov, Alexander Y; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method Journal Article International Journal of Pharmaceutics, 518 (1-2), pp. 50–58, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Dalmoro2017, title = {Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method}, author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine}, url = {http://www.sciencedirect.com/science/article/pii/S037851731631198X}, doi = {10.1016/j.ijpharm.2016.12.056}, year = {2017}, date = {2017-02-25}, journal = {International Journal of Pharmaceutics}, volume = {518}, number = {1-2}, pages = {50\textendash58}, abstract = {In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%. Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%. Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release. |
Barba, Anna Angela; Grassi, Gabriele; Grassi, Mario; Lamberti, Gaetano New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery Journal Article Current Drug Delivery, 14 (2), pp. 156-157, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Barba2017b, title = {New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery}, author = {Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti}, url = {http://gruppotpp.unisa.it/wp-content/uploads/2017/03/01.-Barba-et-al-CDD-142-156-157-2017.pdf http://www.eurekaselect.com/149727}, doi = {10.2174/156720181402170202202808}, year = {2017}, date = {2017-02-09}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {156-157}, abstract = {Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and only if effective delivery systems are available. Among NABDs, small interfering RNAs (siRNAs) show revolutionary potentiality due to the ability to silencing the expression of gene-causing diseases. Thus, siRNA drugs have huge therapeutic potentials, even in the treatment of life threatening diseases. However, the use of siRNAs is limited because of some inconveniences: they are large macromolecules, negatively charged, undergo rapid degradation by plasma enzymes, are subjected to fast renal clearance/hepatic sequestration and can hardly cross cellular membranes. These aspects seriously impair siRNAs usability as therapeutics. To overcome these obstacles, the scientific problem has to be faced out through a multidisciplinary approach, integrating all relevant and necessary expertise. In this Full-Thematic Issue of the Current Drug Delivery, the development of siRNAs delivery approaches is described from different points of view by several research groups, which have been jointly working on the subject in the last years. The Thematic Issue starts with the paper by Chiarappa et al., devoted to describe the potentiality of the Chemical Engineering expertise in the “Bio world” through reminding the foundation of Biological Engineering (BE) that develops, with its current and multidisciplinary approaches, winning strategies in modern research. The concepts of unit operations and transport phenomena, with which chemical engineers are confident, are applied to the description of the biomedical/pharmaceutical world and to the study of siRNAs delivery, in order to get a better understanding and description of how biological systems work. The engineering approach to siRNA delivery is, then, reported analyzing two topics. In particular, the paper by Caccavo et al. deals with the modeling of hydrogel based drug delivery systems, materials widely used in controlled drug delivery, which could be adopted also for siRNAs delivery. Abbiati and Manca report the use of a physiologically-based pharmacokinetic model, useful in order to assess the fate of drugs, including siRNAs, once administered. The novel preparative methods to be used in siRNAs delivery are the subjects of the paper by Bochicchio et al., focusing on both the lipid-based and the polymerbased carriers. More specifically, Dalmoro et al. discuss the use of injectable chitosan/β-glycerophosphate systems, whereas Cavallaro et al. report the uses of polycation-based smart carriers for siRNAs delivery. Advanced testing methods for the study of drug delivery systems and the interactions between delivery systems and living systems are discussed in the paper by D’Apolito et al. and Carf\`{i}-Pavia et al. D’Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carf\`{i}-Pavia et al. concentrate the attention on a novel bioreactor able to mimic the vascular behavior for in-vitro tests of drug delivery. Last but not the least, the medical applications of novel delivery systems and siRNAs are discussed in the paper by Piazza et al., focusing on the delivery of siRNAs by liposomes in order to silence cycline D1 in ex-vivo human tissues. Moreover, the paper by Di Gioia et al., deals with the siRNAs’ based therapies against inflammatory respiratory diseases, while the paper by Farra et al., discusses the role of the transcription factor E2F1 in hepatocellular carcinoma and the opportunity of its silencing by siRNAs. In conclusion, the papers presented strongly indicate that only a multidisciplinary approach can successfully overcome the still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and only if effective delivery systems are available. Among NABDs, small interfering RNAs (siRNAs) show revolutionary potentiality due to the ability to silencing the expression of gene-causing diseases. Thus, siRNA drugs have huge therapeutic potentials, even in the treatment of life threatening diseases. However, the use of siRNAs is limited because of some inconveniences: they are large macromolecules, negatively charged, undergo rapid degradation by plasma enzymes, are subjected to fast renal clearance/hepatic sequestration and can hardly cross cellular membranes. These aspects seriously impair siRNAs usability as therapeutics. To overcome these obstacles, the scientific problem has to be faced out through a multidisciplinary approach, integrating all relevant and necessary expertise. In this Full-Thematic Issue of the Current Drug Delivery, the development of siRNAs delivery approaches is described from different points of view by several research groups, which have been jointly working on the subject in the last years. The Thematic Issue starts with the paper by Chiarappa et al., devoted to describe the potentiality of the Chemical Engineering expertise in the “Bio world” through reminding the foundation of Biological Engineering (BE) that develops, with its current and multidisciplinary approaches, winning strategies in modern research. The concepts of unit operations and transport phenomena, with which chemical engineers are confident, are applied to the description of the biomedical/pharmaceutical world and to the study of siRNAs delivery, in order to get a better understanding and description of how biological systems work. The engineering approach to siRNA delivery is, then, reported analyzing two topics. In particular, the paper by Caccavo et al. deals with the modeling of hydrogel based drug delivery systems, materials widely used in controlled drug delivery, which could be adopted also for siRNAs delivery. Abbiati and Manca report the use of a physiologically-based pharmacokinetic model, useful in order to assess the fate of drugs, including siRNAs, once administered. The novel preparative methods to be used in siRNAs delivery are the subjects of the paper by Bochicchio et al., focusing on both the lipid-based and the polymerbased carriers. More specifically, Dalmoro et al. discuss the use of injectable chitosan/β-glycerophosphate systems, whereas Cavallaro et al. report the uses of polycation-based smart carriers for siRNAs delivery. Advanced testing methods for the study of drug delivery systems and the interactions between delivery systems and living systems are discussed in the paper by D’Apolito et al. and Carfì-Pavia et al. D’Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carfì-Pavia et al. concentrate the attention on a novel bioreactor able to mimic the vascular behavior for in-vitro tests of drug delivery. Last but not the least, the medical applications of novel delivery systems and siRNAs are discussed in the paper by Piazza et al., focusing on the delivery of siRNAs by liposomes in order to silence cycline D1 in ex-vivo human tissues. Moreover, the paper by Di Gioia et al., deals with the siRNAs’ based therapies against inflammatory respiratory diseases, while the paper by Farra et al., discusses the role of the transcription factor E2F1 in hepatocellular carcinoma and the opportunity of its silencing by siRNAs. In conclusion, the papers presented strongly indicate that only a multidisciplinary approach can successfully overcome the still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential. |
Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests Journal Article Current Drug Delivery, 14 (2), pp. 216 - 223, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Characterization @article{Dalmoro2016b, title = { Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests}, author = {Annalisa Dalmoro and Michela Abrami and Barbara Galzerano and Sabrina Bochicchio and Anna Angela Barba and Mario Grassi and Domenico Larobina}, url = {http://gruppotpp.unisa.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-216-223-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/216/ }, doi = {10.2174/1567201813666160721142202}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {216 - 223}, abstract = {Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.}, keywords = {Hydrogel Characterization}, pubstate = {published}, tppubtype = {article} } Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release. |
Chiarappa, Gianluca; Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Barba, Anna Angela; Boisen, Anja; Brucato, Valerio; Ghersi, Giulio; Caccavo, Diego; Cascone, Sara; Caserta, Sergio; Elvassore, Nicola; Giomo, Monica; Guido, Stefano; Lamberti, Gaetano; Larobina, Domenico; Manca, Davide; Marizza, Paolo; Tomaiuolo, Giovanna; Grassi, Gabriele Chemical Engineering in the “BIO” world Journal Article Current Drug Delivery, 14 (2), pp. 158 - 178, 2017. Abstract | Links | BibTeX | Tags: @article{Chiarappa2016, title = {Chemical Engineering in the “BIO” world}, author = {Gianluca Chiarappa and Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Anna Angela Barba and Anja Boisen and Valerio Brucato and Giulio Ghersi and Diego Caccavo and Sara Cascone and Sergio Caserta and Nicola Elvassore and Monica Giomo and Stefano Guido and Gaetano Lamberti and Domenico Larobina and Davide Manca and Paolo Marizza and Giovanna Tomaiuolo and Gabriele Grassi }, url = {http://gruppotpp.unisa.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-158-178-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/158/}, doi = {10.2174/1567201813666160602230550}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {158 - 178}, abstract = {Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update. |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette Drug delivery from hydrogels: a general framework for the release modeling Journal Article Current Drug Delivery, 14 (2), pp. 179 - 189, 2017. Abstract | Links | BibTeX | Tags: Hydrogel Modeling @article{Caccavo2016b, title = {Drug delivery from hydrogels: a general framework for the release modeling}, author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson }, url = {http://gruppotpp.unisa.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/179/}, doi = {10.2174/1567201813666160808102106}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {179 - 189}, abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.}, keywords = {Hydrogel Modeling}, pubstate = {published}, tppubtype = {article} } The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components. |
Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano New preparative approaches for micro and nano drug delivery carriers Journal Article Current Drug Delivery, 14 (2), pp. 203 - 215, 2017. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Bochicchio2016b, title = {New preparative approaches for micro and nano drug delivery carriers}, author = {Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti}, url = {http://gruppotpp.unisa.it/wp-content/uploads/2017/03/05.-Bochicchio-et-al-CDD-142-203-215-2017.pdf http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/203/}, doi = {10.2174/1567201813666160628093724}, year = {2017}, date = {2017-02-08}, issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY}, journal = {Current Drug Delivery}, volume = {14}, number = {2}, pages = {203 - 215}, abstract = {The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown. |
2016 |
Cascone, Sara; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe; d'Amore, Matteo; Barba, Anna Angela Gastrointestinal behavior and ADME phenomena: I. In vitro simulation Journal Article Journal of Drug Delivery Science and Technology, 35 , pp. 272-283, 2016, ISSN: 1773-2247. Abstract | Links | BibTeX | Tags: Biodistribution, In vitro, Pharmacokinetics @article{Cascone2016, title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation}, author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba}, url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659 }, doi = {10.1016/j.jddst.2016.08.002}, issn = {1773-2247}, year = {2016}, date = {2016-10-01}, journal = {Journal of Drug Delivery Science and Technology}, volume = {35}, pages = {272-283}, abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals. This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.}, keywords = {Biodistribution, In vitro, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals. This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed. |
Lamberti, Gaetano; Barba, Anna Angela; Cascone, Sara; Dalmoro, Annalisa; Caccavo, Diego An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications Book Chapter Majee, Sutapa Biswas (Ed.): Emerging Concepts in Analysis and Applications of Hydrogels, Chapter 8, Intech, 2016, ISBN: 978-953-51-2510-5. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling @inbook{Lamberti2016b, title = {An Engineering Point of View on the Use of the Hydrogels for Pharmaceutical and Biomedical Applications}, author = {Gaetano Lamberti and Anna Angela Barba and Sara Cascone and Annalisa Dalmoro and Diego Caccavo}, editor = {Sutapa Biswas Majee}, url = {http://www.intechopen.com/books/emerging-concepts-in-analysis-and-applications-of-hydrogels/an-engineering-point-of-view-on-the-use-of-the-hydrogels-for-pharmaceutical-and-biomedical-applicati}, doi = {10.5772/64299 }, isbn = {978-953-51-2510-5}, year = {2016}, date = {2016-08-24}, booktitle = {Emerging Concepts in Analysis and Applications of Hydrogels}, publisher = {Intech}, chapter = {8}, abstract = {In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences.}, keywords = {Hydrogel Characterization, Hydrogel Modeling}, pubstate = {published}, tppubtype = {inbook} } In this chapter, the modern uses of hydrogels in pharmaceutical and biomedical applications are revised following an engineering point of view, i.e. focusing the attention on material properties and process conditions. The chapter discusses the applications following the increase in scale‐size. First, the nanoscale systems, i.e. hydrogel nanoparticles (HNPs), are analysed in terms of preparative approaches (polymerization methods and uses of preformed polymers) and with a brief mention of the future trends in the field. Secondly, systems based on hydrogel microparticles (HMPs) are examined following the same scheme (polymerization methods, uses of preformed polymers, a mention of novel and future trends). Thirdly, and last but not the least, the hydrogel‐based drug delivery systems (macroscopic HB‐DDSs) are presented, focusing in particular on tablets made of hydrogels, discussing the characterization methods and on the modelling approaches used to describe their behaviour. Other macroscopic systems are also discussed in brief. Even if the vastness of the field makes its discussion impossible in a single chapter, the presented material can be a good starting point to study the uses of hydrogels in pharmaceutical and biomedical sciences. |
Lamberti, Gaetano; Cascone, Sara; Marra, Francesco; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Gastrointestinal behavior and ADME phenomena: II. in silico simulation Journal Article Journal of Drug Delivery Science and Technology, 35 , pp. 165-171, 2016, ISSN: 1773-2247. Abstract | Links | BibTeX | Tags: In silico, Pharmacokinetics @article{Lamberti2016, title = {Gastrointestinal behavior and ADME phenomena: II. in silico simulation}, author = {Gaetano Lamberti and Sara Cascone and Francesco Marra and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S1773224716302118}, doi = {10.1016/j.jddst.2016.06.014}, issn = {1773-2247}, year = {2016}, date = {2016-07-04}, journal = {Journal of Drug Delivery Science and Technology}, volume = {35}, pages = {165-171}, abstract = {The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena. This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications.}, keywords = {In silico, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena. This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications. |
Piazza, Ornella; Cascone, Sara; Sessa, Linda; De Robertis, Edoardo ; Lamberti, Gaetano The effect of liver esterases and temperature on remifentanil degradation in vitro Journal Article International Journal of Pharmaceutics, 510 (1), pp. 359–364, 2016. Abstract | Links | BibTeX | Tags: In vitro, Pharmacokinetics @article{Piazza2016b, title = {The effect of liver esterases and temperature on remifentanil degradation in vitro}, author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191}, doi = {10.1016/j.ijpharm.2016.06.043}, year = {2016}, date = {2016-07-04}, journal = {International Journal of Pharmaceutics}, volume = {510}, number = {1}, pages = {359\textendash364}, abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.}, keywords = {In vitro, Pharmacokinetics}, pubstate = {published}, tppubtype = {article} } Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures. |
Dalmoro, Annalisa; Barba, Anna Angela; Grassi, Gabriele; Grassi, Mario; Lamberti, Gaetano In situ coronary stent paving by Pluronic F127–alginate gel blends: formulation and erosion tests Journal Article Journal of Biomedical Materials Research Part B: Applied Biomaterials, 104 (5), pp. 1013-22, 2016. Abstract | Links | BibTeX | Tags: coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends @article{Dalmoro2016b, title = {In situ coronary stent paving by Pluronic F127\textendashalginate gel blends: formulation and erosion tests}, author = {Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti}, url = {http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33425/abstract;jsessionid=31C6676EE270B6362CB149075EE37B5F.f01t01}, doi = {10.1002/jbm.b.33425}, year = {2016}, date = {2016-07-01}, journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials}, volume = {104}, number = {5}, pages = {1013-22}, abstract = {In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.}, keywords = {coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends}, pubstate = {published}, tppubtype = {article} } In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015. |
Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Gabriele; Lamberti, Gaetano Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation Journal Article LWT - Food Science and Technology, 69 , pp. 9-16, 2016. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @article{Bochicchio2016, title = {Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation}, author = {Sabrina Bochicchio and Anna Angela Barba and Gabriele Grassi and Gaetano Lamberti}, url = {http://www.sciencedirect.com/science/article/pii/S0023643816300251}, doi = {10.1016/j.lwt.2016.01.025}, year = {2016}, date = {2016-06-01}, journal = {LWT - Food Science and Technology}, volume = {69}, pages = {9-16}, abstract = {In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.}, keywords = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions. |