Le pubblicazioni dei componenti del gruppo di ricerca.
2017
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
In: International Journal of Pharmaceutics, vol. 528, no 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
In: 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
In: Natural Product Communications, vol. 12, no 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
https://www.gruppotpp.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
In: Natural Product Communications, vol. 12, no 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
https://www.gruppotpp.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.
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.
Simone, Veronica De; 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
In: New Journal of Chemistry, vol. 41, no 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
In: Materials Science and Engineering: C, vol. 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
In: Carbohydrate Polymers, vol. 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.
Bochicchio, Sabrina; Dapas, Barbara; Russo, Ilaria; Ciacci, Carolina; Piazza, Ornella; Smedt, Stefan De; 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
In: International Journal of Pharmaceutics, vol. 525, no 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.
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.
Barba, Anna Angela; Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Chiarappa, Gianluca; Abrami, Michela; Grassi, Gabriele; Grassi, Mario; Tomaiuolo, Giovanna; Guido, Stefano; Brucato, Valerio; Pavia, Francesco Carfì; Ghersi, Giulio; Carrubba, Vincenzo La; Abbiati, Roberto Andrea; Manca, Davide
Engineering approaches in siRNA delivery Journal Article
In: International Journal of Pharmaceutics, vol. 525, no 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.
Lamberti, Gaetano
Delivery of siRNAs Journal Article
In: International Journal of Pharmaceutics, vol. 525, no 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
In: International Journal of Pharmaceutics, vol. 528, no 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
In: British Journal of Pharmacology, vol. 174, no 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.
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
In: International Journal of Pharmaceutics, vol. 518, no 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.
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
In: Current Drug Delivery, vol. 14, no 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 = {https://www.gruppotpp.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.
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.
Piazza, Ornella; Russo, Ilaria; Bochicchio, Sabrina; Barba, Anna Angela; Lamberti, Gaetano; Zeppa, Pio; Crescenzo, Vincenzo Di; Carrizzo, Albino; Vecchione, Carmine; Ciacci, Carolina
Cyclin D1 gene silencing by siRNA in ex vivo human tissues cultures Journal Article
In: Current Drug Delivery, vol. 14, no 2, pp. 246 - 252, 2017.
Abstract | Links | BibTeX | Tags:
@article{Piazza2016,
title = {Cyclin D1 gene silencing by siRNA in ex vivo human tissues cultures},
author = {Ornella Piazza and Ilaria Russo and Sabrina Bochicchio and Anna Angela Barba and Gaetano Lamberti and Pio Zeppa and Vincenzo {Di Crescenzo} and Albino Carrizzo and Carmine Vecchione and Carolina Ciacci},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/10.-Piazza-et-al-CDD-142-246-252-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/246/},
doi = {10.2174/1567201813666160512150710},
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 = {246 - 252},
abstract = {Background. Short interfering RNAs (siRNAs) are double-stranded RNA molecules able to specifically targeting genes products responsible for human diseases. Cyclin D1 (CyD1) is a cell cycle-regulatory molecule, up-regulated at sites of inflammation in several tissues. CyD1 is a very interesting potential target in lung and colon inflammatory diseases.
Objective. The aim of this paper was testing CyD1 expression in human lung and colon tissues after the application of an inflammatory stimulus, and verifying its gene silencing by using siRNA for CyD1 (siCyD1).
Method. Colon and pulmonary biopsies were treated with siCyD1 by using two different transfection carriers: a) invivofectamine and b) ad hoc produced nanoliposomes. After 24 hours of incubation with nanoliposomes encapsulating siRNA or invivofectamine-CyD1siRNA, in presence or absence of EC-LPS, we analysed the protein expression of CyD1 through Western-Blotting.
Results. After EC-LPS treatment, in both colon and pulmonary biopsies, an overexpression of CyD1was found (about 64% and 40% respectively). Invivofectamine-CyD1 siRNA reduced the expression of CyD1 approximately by 46% compared to the basal condition, and by around 65% compared to EC-LPS treated colon samples. In lung, following invivofectamine siRNA silencing in the presence of EC-LPS, no reduction was observed.
Ad hoc nanoliposomes were able to enter colon and lung tissues, but CyD1 silencing was reported in 2 colon samples out of 4 and no efficacy was demonstrated in the only lung sample we studied.
Conclusion. It is possible to silencing Cyclin D1 expression in vitro “organ culture” model. Our preliminary results encourage further investigations, using different siRNA concentrations delivered by nanoliposomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background. Short interfering RNAs (siRNAs) are double-stranded RNA molecules able to specifically targeting genes products responsible for human diseases. Cyclin D1 (CyD1) is a cell cycle-regulatory molecule, up-regulated at sites of inflammation in several tissues. CyD1 is a very interesting potential target in lung and colon inflammatory diseases.
Objective. The aim of this paper was testing CyD1 expression in human lung and colon tissues after the application of an inflammatory stimulus, and verifying its gene silencing by using siRNA for CyD1 (siCyD1).
Method. Colon and pulmonary biopsies were treated with siCyD1 by using two different transfection carriers: a) invivofectamine and b) ad hoc produced nanoliposomes. After 24 hours of incubation with nanoliposomes encapsulating siRNA or invivofectamine-CyD1siRNA, in presence or absence of EC-LPS, we analysed the protein expression of CyD1 through Western-Blotting.
Results. After EC-LPS treatment, in both colon and pulmonary biopsies, an overexpression of CyD1was found (about 64% and 40% respectively). Invivofectamine-CyD1 siRNA reduced the expression of CyD1 approximately by 46% compared to the basal condition, and by around 65% compared to EC-LPS treated colon samples. In lung, following invivofectamine siRNA silencing in the presence of EC-LPS, no reduction was observed.
Ad hoc nanoliposomes were able to enter colon and lung tissues, but CyD1 silencing was reported in 2 colon samples out of 4 and no efficacy was demonstrated in the only lung sample we studied.
Conclusion. It is possible to silencing Cyclin D1 expression in vitro “organ culture” model. Our preliminary results encourage further investigations, using different siRNA concentrations delivered by nanoliposomes.
Objective. The aim of this paper was testing CyD1 expression in human lung and colon tissues after the application of an inflammatory stimulus, and verifying its gene silencing by using siRNA for CyD1 (siCyD1).
Method. Colon and pulmonary biopsies were treated with siCyD1 by using two different transfection carriers: a) invivofectamine and b) ad hoc produced nanoliposomes. After 24 hours of incubation with nanoliposomes encapsulating siRNA or invivofectamine-CyD1siRNA, in presence or absence of EC-LPS, we analysed the protein expression of CyD1 through Western-Blotting.
Results. After EC-LPS treatment, in both colon and pulmonary biopsies, an overexpression of CyD1was found (about 64% and 40% respectively). Invivofectamine-CyD1 siRNA reduced the expression of CyD1 approximately by 46% compared to the basal condition, and by around 65% compared to EC-LPS treated colon samples. In lung, following invivofectamine siRNA silencing in the presence of EC-LPS, no reduction was observed.
Ad hoc nanoliposomes were able to enter colon and lung tissues, but CyD1 silencing was reported in 2 colon samples out of 4 and no efficacy was demonstrated in the only lung sample we studied.
Conclusion. It is possible to silencing Cyclin D1 expression in vitro “organ culture” model. Our preliminary results encourage further investigations, using different siRNA concentrations delivered by nanoliposomes.
D'Apolito, Rosa; Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; Guido, Stefano; Tomaiuolo, Giovanna
Microfluidic investigation of the effect of liposome surface charge on drug delivery in microcirculation Journal Article
In: Current Drug Delivery, vol. 14, no 2, pp. 231 - 238, 2017.
Abstract | Links | BibTeX | Tags:
@article{D'Apolito2016,
title = {Microfluidic investigation of the effect of liposome surface charge on drug delivery in microcirculation},
author = {Rosa D'Apolito and Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Stefano Guido and Giovanna Tomaiuolo},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/08.-DApolito-et-al-CDD-142-231-238-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/231/},
doi = {10.2174/1567201813666160813172047},
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 = {231 - 238},
abstract = {Nano-carrier drug transport in blood microcirculation is one of the hotspots of current research in drug development due to many advantages over traditional therapies, such as reduced side-effects, target delivery, controlled release, improved pharmacokinetics and therapeutic index. Despite the substantial efforts made in the design of nanotherapeutics, the big majority of the used strategies failed to overcome the biological barriers to drug transport encountered in human microvasculature, such as transport by blood flow via the microcirculatory network and margination, the mechanism according to which particles migrate along vessel radius to the wall. In fact, drug transport efficiency in microvasculature is affected by both the particulate nature of blood and drug carrier properties, such as size, shape and surface charge.
In this work, the effect of the surface charge of liposomes on their margination in blood flow in microcapillaries was experimentally evaluated. By high-speed video microscopy and image analysis it was found that the two custom-made liposomes (one neuter and the other positively charged) tend to drift laterally, moving towards the wall and accumulating in the cell-free layer. In particular, neuter and cationic liposomes showed a comparable margination propensity, suggesting that the presence of blood cells governs the flow behavior independently on liposome surface charge.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nano-carrier drug transport in blood microcirculation is one of the hotspots of current research in drug development due to many advantages over traditional therapies, such as reduced side-effects, target delivery, controlled release, improved pharmacokinetics and therapeutic index. Despite the substantial efforts made in the design of nanotherapeutics, the big majority of the used strategies failed to overcome the biological barriers to drug transport encountered in human microvasculature, such as transport by blood flow via the microcirculatory network and margination, the mechanism according to which particles migrate along vessel radius to the wall. In fact, drug transport efficiency in microvasculature is affected by both the particulate nature of blood and drug carrier properties, such as size, shape and surface charge.
In this work, the effect of the surface charge of liposomes on their margination in blood flow in microcapillaries was experimentally evaluated. By high-speed video microscopy and image analysis it was found that the two custom-made liposomes (one neuter and the other positively charged) tend to drift laterally, moving towards the wall and accumulating in the cell-free layer. In particular, neuter and cationic liposomes showed a comparable margination propensity, suggesting that the presence of blood cells governs the flow behavior independently on liposome surface charge.
In this work, the effect of the surface charge of liposomes on their margination in blood flow in microcapillaries was experimentally evaluated. By high-speed video microscopy and image analysis it was found that the two custom-made liposomes (one neuter and the other positively charged) tend to drift laterally, moving towards the wall and accumulating in the cell-free layer. In particular, neuter and cationic liposomes showed a comparable margination propensity, suggesting that the presence of blood cells governs the flow behavior independently on liposome surface charge.
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
In: Current Drug Delivery, vol. 14, no 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 = {https://www.gruppotpp.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.
Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
New preparative approaches for micro and nano drug delivery carriers Journal Article
In: Current Drug Delivery, vol. 14, no 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 = {https://www.gruppotpp.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.
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.
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
In: Current Drug Delivery, vol. 14, no 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 = {https://www.gruppotpp.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.
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Drug delivery from hydrogels: a general framework for the release modeling Journal Article
In: Current Drug Delivery, vol. 14, no 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 = {https://www.gruppotpp.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.
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
In: Journal of Drug Delivery Science and Technology, vol. 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.
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
In: 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.
Piazza, Ornella; Cascone, Sara; Sessa, Linda; Robertis, Edoardo De; Lamberti, Gaetano
The effect of liver esterases and temperature on remifentanil degradation in vitro Journal Article
In: International Journal of Pharmaceutics, vol. 510, no 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.
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
In: Journal of Drug Delivery Science and Technology, vol. 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.
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.
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
In: Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 104, no 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
In: LWT - Food Science and Technology, vol. 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.
Dalmoro, Annalisa; Sitenkov, Alexander Y.; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I.
Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell–core microparticles Journal Article
In: Journal of Applied Polymer Science, vol. 133, no 42976, 2016.
Abstract | Links | BibTeX | Tags: Micro and Nano Vectors
@article{Dalmoro2016,
title = {Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell\textendashcore microparticles},
author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
url = {http://onlinelibrary.wiley.com/doi/10.1002/app.42976/abstract},
doi = {10.1002/app.42976},
year = {2016},
date = {2016-02-10},
journal = {Journal of Applied Polymer Science},
volume = {133},
number = {42976},
abstract = {In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell\textendashcore microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization\textendashpolyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers. },
keywords = {Micro and Nano Vectors},
pubstate = {published},
tppubtype = {article}
}
In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell–core microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization–polyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers.
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Larsson, Anette
Swellable Hydrogel-based Systems for Controlled Drug Delivery Book Chapter
In: Sezer, Ali Demir (Ed.): Smart Drug Delivery System, Chapter 10, Intech, 2016, ISBN: 978-953-51-2247-0.
Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling
@inbook{Caccavo2016b,
title = {Swellable Hydrogel-based Systems for Controlled Drug Delivery},
author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},
editor = {Ali Demir Sezer},
url = {http://www.intechopen.com/books/smart-drug-delivery-system/swellable-hydrogel-based-systems-for-controlled-drug-delivery#exportas},
doi = {10.5772/61792},
isbn = {978-953-51-2247-0},
year = {2016},
date = {2016-02-10},
booktitle = {Smart Drug Delivery System},
publisher = {Intech},
chapter = {10},
abstract = {The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass\textendashrubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.},
keywords = {Hydrogel Characterization, Hydrogel Modeling},
pubstate = {published},
tppubtype = {inbook}
}
The controlled delivery of drugs can be effectively obtained using systems based on hydrogels. Tablets, to be orally administered, represent the simplest and the most traditional dosage systems based on hydrogel. Their formulation and preparation require to mix and to compress, in proper ratios, various excipients, including a swellable polymer and a drug. Carriers for controlled release systems are usually cross-linked polymers able to form hydrogels that show peculiar release mechanisms, where both diffusion and tablet swelling play important roles.When a dry swellable hydrogel-based matrix is immersed in a physiological fluid, this starts to penetrate inside the polymeric hydrophilic matrix. When a certain solvent concentration is reached, the polymeric chains unfold due to a glass–rubber transition, and a gel-like layer is formed. In the swollen region, the drug molecules can easily diffuse toward the outer dissolution medium, once they are dissolved. The polymer network became extremely hydrated where the swollen matrix is in contact with the outer medium, and processes like chain disentanglement take place, “eroding” the matrix.This chapter is focused on the analysis of the state of the art about the uses of carriers for controlled release systems composed by hydrogel-based matrices. This analysis has been performed studying in deep both the experimental and the modeling techniques which have been investigated over the years to characterize all the phenomena involved during the drug release.
Apicella, Pietro; Cascone, Sara; Santis, Felice De; Lamberti, Gaetano
Iron Chelates: Production Processes and Reaction Evolution Analysis Journal Article
In: Chemical Engineering Communications, 2016.
Abstract | Links | BibTeX | Tags: Chelating Agents
@article{Apicella2016,
title = {Iron Chelates: Production Processes and Reaction Evolution Analysis},
author = {Pietro Apicella and Sara Cascone and Felice De Santis and Gaetano Lamberti },
url = {http://www.tandfonline.com/doi/abs/10.1080/00986445.2015.1114476?journalCode=gcec20},
doi = {10.1080/00986445.2015.1114476},
year = {2016},
date = {2016-01-16},
journal = {Chemical Engineering Communications},
abstract = {Nowadays, fertilization using synthetic chelates is the most common technique to solve the iron chlorosis, a disease which affects the plants growth. The ethylenediamine-N,N’-bis(o-hydroxyphenyl) acetic acid (EDDHA) is among the most efficient iron chelating agents. To produce EDDHA, a reaction has been performed using as reactants: phenol, ethylenediamine, glyoxylic acid, and sodium hydroxide. To study the reaction kinetics, samples have been withdrawn from the reactor during the reaction and the kinetics has been quantified, evaluating the yield evolution during the reaction phase. This study has been useful to optimize the reaction time. Then, a catalyst has been added to the reaction mixture, to analyze its effect on the reaction evolution. Comparing the reaction evolution of the non-catalyzed and the catalyzed reaction protocols, two main results have to be highlighted: the time to reach the final yield is lower than the one proposed in literature and the used catalyst has a minimum effect on the reaction rate.},
keywords = {Chelating Agents},
pubstate = {published},
tppubtype = {article}
}
Nowadays, fertilization using synthetic chelates is the most common technique to solve the iron chlorosis, a disease which affects the plants growth. The ethylenediamine-N,N’-bis(o-hydroxyphenyl) acetic acid (EDDHA) is among the most efficient iron chelating agents. To produce EDDHA, a reaction has been performed using as reactants: phenol, ethylenediamine, glyoxylic acid, and sodium hydroxide. To study the reaction kinetics, samples have been withdrawn from the reactor during the reaction and the kinetics has been quantified, evaluating the yield evolution during the reaction phase. This study has been useful to optimize the reaction time. Then, a catalyst has been added to the reaction mixture, to analyze its effect on the reaction evolution. Comparing the reaction evolution of the non-catalyzed and the catalyzed reaction protocols, two main results have to be highlighted: the time to reach the final yield is lower than the one proposed in literature and the used catalyst has a minimum effect on the reaction rate.
Abbiati, Roberto Andrea; Lamberti, Gaetano; Grassi, Mario; Trotta, Francesco; Manca, Davide
Definition and validation of a patient-individualized physiologically-based pharmacokinetic model Journal Article
In: Computers & Chemical Engineering, vol. 84 , pp. 394-408, 2016, ISSN: 00981354.
Abstract | Links | BibTeX | Tags: Biodistribution, In silico, Model reduction and lumping, Personalized parameters, Pharmacokinetic models, Pharmacokinetics, Physiologically based modeling, Remifentanil.
@article{Abbiati2015,
title = {Definition and validation of a patient-individualized physiologically-based pharmacokinetic model},
author = { Roberto Andrea Abbiati and Gaetano Lamberti and Mario Grassi and Francesco Trotta and Davide Manca},
url = {http://www.sciencedirect.com/science/article/pii/S0098135415003130},
doi = {10.1016/j.compchemeng.2015.09.018},
issn = {00981354},
year = {2016},
date = {2016-01-04},
journal = {Computers \& Chemical Engineering},
volume = {84 },
pages = {394-408},
abstract = {Pharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentration prediction in living beings. The development of a reduced physiologically-based pharmacokinetic model (PBPK model), is performed by lumping organs and tissues with comparable characteristics respect to drug distribution phenomena. The proposed reduced model comprises eight differential equations and 18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alternatively: (i) individualized according to literature correlations on the physiological features of each patient; (ii) assigned as constants based on the features of either human body or drug properties; (iii) regressed respect to experimental data. The model predictive capability is validated with experimental blood concentrations of remifentanil, an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30$mu$g/kg) to mixed groups of patients. Concentration profiles for the four simulated doses reveal a rather good consistency with experimental data.},
keywords = {Biodistribution, In silico, Model reduction and lumping, Personalized parameters, Pharmacokinetic models, Pharmacokinetics, Physiologically based modeling, Remifentanil.},
pubstate = {published},
tppubtype = {article}
}
Pharmacokinetic modeling based on a mechanistic approach is a promising tool for drug concentration prediction in living beings. The development of a reduced physiologically-based pharmacokinetic model (PBPK model), is performed by lumping organs and tissues with comparable characteristics respect to drug distribution phenomena. The proposed reduced model comprises eight differential equations and 18 adaptive parameters. To improve the quality of the PBPK model these adaptive parameters are alternatively: (i) individualized according to literature correlations on the physiological features of each patient; (ii) assigned as constants based on the features of either human body or drug properties; (iii) regressed respect to experimental data. The model predictive capability is validated with experimental blood concentrations of remifentanil, an analgesic drug, administered via bolus injection with four doses (2, 5, 15, 30$mu$g/kg) to mixed groups of patients. Concentration profiles for the four simulated doses reveal a rather good consistency with experimental data.
Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano
Modeling capillary formation in calcium and copper alginate gels Journal Article
In: Materials Science and Engineering: C, vol. 58, pp. 442–449, 2016, ISSN: 09284931.
Abstract | Links | BibTeX | Tags: Alginate, Gel capillaries, Hydrogel Characterization, Hydrogel Modeling, Ionotropic gelation, Modeling
@article{Caccavo2016,
title = {Modeling capillary formation in calcium and copper alginate gels},
author = { Diego Caccavo and Anna Str\"{o}m and Anette Larsson and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0928493115302940},
doi = {10.1016/j.msec.2015.08.040},
issn = {09284931},
year = {2016},
date = {2016-01-01},
journal = {Materials Science and Engineering: C},
volume = {58},
pages = {442--449},
abstract = {Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.},
keywords = {Alginate, Gel capillaries, Hydrogel Characterization, Hydrogel Modeling, Ionotropic gelation, Modeling},
pubstate = {published},
tppubtype = {article}
}
Alginate solutions in the presence of bivalent ions can form ionic cross-linked gels. In particular gelation conditions the gel structure can be characterized by great anisotropy with the presence of straight capillaries along a preferential direction. These materials can find applications mainly in high-tech sectors, like tissue engineering, where the gel characteristics play a crucial role. Despite the need of mastering the capillary formation and properties, the process remains a poorly known problem, and its development is left to trial and error procedures. In this work a quantitative approach to the description of the capillary formation process has been developed. The theory proposed by Treml et al. (2003) has been implemented and extended to an alginate different from the one used in that study and two different ions (calcium and copper). Some of the model parameters have been derived through simple measurements; others have been scaled using proper scaling equations. Experiments have been performed in different gelation conditions, varying alginate and ionic solution concentrations, to highlight the effects of these parameters on the anisotropic structure and to validate the model. In all the analyses done, the model has performed nicely showing a good reliability in the prediction of gel characteristics like capillary formation, capillary length and process time.
2015
Lamberti, Gaetano
How mathematical modeling tools are helping the pharmaceutical sciences Journal Article
In: International Journal of Pharmaceutics, vol. 496, no 2, pp. 157-158, 2015, ISSN: 0378-5173, (Editorial).
Abstract | Links | BibTeX | Tags: Controlled drug release, Mathematical modeling, Pharmacokinetics
@article{Lamberti2015,
title = {How mathematical modeling tools are helping the pharmaceutical sciences},
author = {Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315006377},
doi = {10.1016/j.ijpharm.2015.11.003},
issn = {0378-5173},
year = {2015},
date = {2015-12-30},
journal = {International Journal of Pharmaceutics},
volume = {496},
number = {2},
pages = {157-158},
abstract = {No abstract.},
note = {Editorial},
keywords = {Controlled drug release, Mathematical modeling, Pharmacokinetics},
pubstate = {published},
tppubtype = {article}
}
No abstract.
Caccavo, Diego; Lamberti, Gaetano; Cascone, Sara; Barba, Anna Angela; Larsson, Anette
Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment Journal Article
In: Carbohydrate Polymers, vol. 131, pp. 41–49, 2015, ISSN: 01448617.
Abstract | Links | BibTeX | Tags: Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport
@article{Caccavo2015b,
title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment},
author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson},
url = {http://www.sciencedirect.com/science/article/pii/S0144861715004476},
doi = {10.1016/j.carbpol.2015.05.041},
issn = {01448617},
year = {2015},
date = {2015-10-01},
journal = {Carbohydrate Polymers},
volume = {131},
pages = {41--49},
abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.},
keywords = {Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport},
pubstate = {published},
tppubtype = {article}
}
The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.
Cavallaro, Gennara; Craparo, Emanuela Fabiola; Sardo, Carla; Lamberti, Gaetano; Barba, Anna Angela; Dalmoro, Annalisa
PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions. Journal Article
In: International journal of pharmaceutics, vol. 495, no 2, pp. 719-727, 2015, ISSN: 1873-3476.
Abstract | Links | BibTeX | Tags: Biopolymer, Micro and Nano Vectors, multiple emulsions, nanoparticles, solvent evaporation
@article{Cavallaro2015,
title = {PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions.},
author = { Gennara Cavallaro and Emanuela Fabiola Craparo and Carla Sardo and Gaetano Lamberti and Anna Angela Barba and Annalisa Dalmoro},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315302519},
doi = {10.1016/j.ijpharm.2015.09.050},
issn = {1873-3476},
year = {2015},
date = {2015-09-01},
journal = {International journal of pharmaceutics},
volume = {495},
number = {2},
pages = {719-727},
abstract = {Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the $alpha$,$beta$-poly(N-2-hydroxyethyl)-DL-aspartamide - polylactic acid (PHEA - PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with $alpha$ tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total $alpha$ tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi- long term release drug delivery systems.},
keywords = {Biopolymer, Micro and Nano Vectors, multiple emulsions, nanoparticles, solvent evaporation},
pubstate = {published},
tppubtype = {article}
}
Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the $alpha$,$beta$-poly(N-2-hydroxyethyl)-DL-aspartamide - polylactic acid (PHEA - PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with $alpha$ tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total $alpha$ tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi- long term release drug delivery systems.
Abrahmsén-Alami, Susanna; Caccavo, Diego; Lamberti, Gaetano; Barba, Anna Angela; Viridén, Anna; Larsson, Anette
Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach Journal Article
In: AstraZeneca Internal Journal, pp. 1-2, 2015.
Abstract | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling
@article{Abrahms\'{e}n-Alami2015,
title = {Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach},
author = {Susanna Abrahms\'{e}n-Alami and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Anna Virid\'{e}n and Anette Larsson},
year = {2015},
date = {2015-09-01},
journal = {AstraZeneca Internal Journal},
pages = {1-2},
abstract = {In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior \textendash as well as for the design \textendash of the tablets based on hydrogels.},
keywords = {Hydrogel Characterization, Hydrogel Modeling},
pubstate = {published},
tppubtype = {article}
}
In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior – as well as for the design – of the tablets based on hydrogels.
Caccavo, Diego; Cascone, Sara; Bochicchio, Sabrina; Lamberti, Gaetano; Dalmoro, Annalisa; Barba, Anna Angela
Hydrogels-based matrices behavior: experimental and modeling description Proceedings Article
In: 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
BibTeX | Tags:
@inproceedings{Caccavo:aa,
title = {Hydrogels-based matrices behavior: experimental and modeling description},
author = {Diego Caccavo and Sara Cascone and Sabrina Bochicchio and Gaetano Lamberti and Annalisa Dalmoro and Anna Angela Barba},
year = {2015},
date = {2015-07-26},
booktitle = {42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Dalmoro, Annalisa; Bochicchio, Sabrina; Lamberti, Gaetano; Sala, Marina; Campiglia, Pietro
Ultrasonic assisted production of nanoliposomes as peptide delivery vectors Proceedings Article
In: 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
BibTeX | Tags:
@inproceedings{Dalmoro:ab,
title = {Ultrasonic assisted production of nanoliposomes as peptide delivery vectors},
author = { Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Marina Sala and Pietro Campiglia},
year = {2015},
date = {2015-07-26},
booktitle = {42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Dalmoro, Annalisa; Cavallaro, Gennara; Craparo, Emanuela Fabiola; Sardo, Carla; Lamberti, Gaetano; Barba, Anna Angela
Production of polyaspartamide based nanovectors by the method of solvent evaporation from ultrasound-made multiple emulsions Proceedings Article
In: 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
BibTeX | Tags:
@inproceedings{Dalmoro:ac,
title = {Production of polyaspartamide based nanovectors by the method of solvent evaporation from ultrasound-made multiple emulsions},
author = { Annalisa Dalmoro and Gennara Cavallaro and Emanuela Fabiola Craparo and Carla Sardo and Gaetano Lamberti and Anna Angela Barba},
year = {2015},
date = {2015-07-26},
booktitle = {42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Grassi, Mario; Abrami, Michela; Abbiati, Roberto Andrea; Posocco, Bianca; Barba, Anna Angela; Lamberti, Gaetano; Manca, Davide; Voinovich, Dario; Grassi, Gabriele
MASS BALANCE: AN OLD CONCEPT FOR THE NEW CHALLENGES PROPOSED BY PERSONALIZED MEDICINE Proceedings Article
In: The 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
BibTeX | Tags:
@inproceedings{Grassi:aa,
title = {MASS BALANCE: AN OLD CONCEPT FOR THE NEW CHALLENGES PROPOSED BY PERSONALIZED MEDICINE},
author = { Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Bianca Posocco and Anna Angela Barba and Gaetano Lamberti and Davide Manca and Dario Voinovich and Gabriele Grassi},
year = {2015},
date = {2015-07-26},
booktitle = {The 42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Caccavo, Diego; Apicella, Pietro; Cascone, Sara; Dalmoro, Annalisa; Lamberti, Gaetano; Barba, Anna Angela
Hydrogels-based systems for controlled release in agricultural applications Proceedings Article
In: 42nd Annual Meeting & Exposition of the Controlled Release Society, 2015.
BibTeX | Tags: Hydrogel Characterization
@inproceedings{Caccavo2015b,
title = {Hydrogels-based systems for controlled release in agricultural applications},
author = {Diego Caccavo and Pietro Apicella and Sara Cascone and Annalisa Dalmoro and Gaetano Lamberti and Anna Angela Barba },
year = {2015},
date = {2015-07-26},
booktitle = {42nd Annual Meeting \& Exposition of the Controlled Release Society},
keywords = {Hydrogel Characterization},
pubstate = {published},
tppubtype = {inproceedings}
}
Bochicchio, Sabrina; Dalmoro, Annalisa; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
dsDNA encapsulating in nanoliposomal structures towards gene therapies Proceedings Article
In: 1st International Congress οf Controlled Release Society - Greek Local Chapter, 2015.
BibTeX | Tags:
@inproceedings{Bochicchio:ab,
title = {dsDNA encapsulating in nanoliposomal structures towards gene therapies},
author = { Sabrina Bochicchio and Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2015},
date = {2015-05-27},
booktitle = {1st International Congress οf Controlled Release Society - Greek Local Chapter},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Dalmoro, Annalisa; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Enteric dosage systems by ultrasonic atomization of natural biopolymers coupled to polyelectrolyte complexation Proceedings Article
In: 1st International Congress οf Controlled Release Society - Greek Local Chapter, 2015.
BibTeX | Tags:
@inproceedings{Dalmoro:af,
title = {Enteric dosage systems by ultrasonic atomization of natural biopolymers coupled to polyelectrolyte complexation},
author = { Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2015},
date = {2015-05-27},
booktitle = {1st International Congress οf Controlled Release Society - Greek Local Chapter},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
Cascone, Sara; Piazza, Ornella; Lamberti, Gaetano; Barba, Anna Angela; Abbiati, Roberto Andrea; Manca, Davide
PHARMACOKINETICS OF REMIFENTANIL: METABOLISM AND MODELING Proceedings Article
In: 1st International Congress of Controlled Release Society - Greek Local Chapter, 2015.
BibTeX | Tags: In silico, Pharmacokinetics
@inproceedings{Cascone:aa,
title = {PHARMACOKINETICS OF REMIFENTANIL: METABOLISM AND MODELING},
author = {Sara Cascone and Ornella Piazza and Gaetano Lamberti and Anna Angela Barba and Roberto Andrea Abbiati and Davide Manca},
year = {2015},
date = {2015-05-27},
booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter},
keywords = {In silico, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Hydrogel-Based CRSs Analyses: Testing And Modeling Proceedings Article
In: 1st International Congress of Controlled Release Society - Greek Local Chapter, pp. 1–1, 1st International Congress of Controlled Release Society, Athens (Greece), 2015.
BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling
@inproceedings{caccavo2015b,
title = {Hydrogel-Based CRSs Analyses: Testing And Modeling},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2015},
date = {2015-05-01},
booktitle = {1st International Congress of Controlled Release Society - Greek Local Chapter},
pages = {1--1},
publisher = {1st International Congress of Controlled Release Society},
address = {Athens (Greece)},
keywords = {Hydrogel Characterization, Hydrogel Modeling},
pubstate = {published},
tppubtype = {inproceedings}
}
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article
In: International journal of pharmaceutics, vol. 486, no 1-2, pp. 144–152, 2015, ISSN: 1873-3476.
Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake
@article{Caccavo2015a,
title = {Controlled drug release from hydrogel-based matrices: Experiments and modeling.},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315002707},
doi = {10.1016/j.ijpharm.2015.03.054},
issn = {1873-3476},
year = {2015},
date = {2015-03-01},
journal = {International journal of pharmaceutics},
volume = {486},
number = {1-2},
pages = {144--152},
abstract = {Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.},
keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake},
pubstate = {published},
tppubtype = {article}
}
Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.
Dalmoro, Annalisa; Barba, Anna Angela; Caputo, Silvestro
Qualità ed efficienza con l’uso di microonde nel trattamento di alimenti Journal Article
In: Tecnologie Alimentari, vol. 2, pp. 32-36, 2015.
Abstract | Links | BibTeX | Tags: Tecnagri
@article{Dalmoro2015b,
title = {Qualit\`{a} ed efficienza con l’uso di microonde nel trattamento di alimenti},
author = {Annalisa Dalmoro and Anna Angela Barba and Silvestro Caputo },
url = {https://www.gruppotpp.it/wp-content/uploads/2015/12/dalmoro_et_al_ta_2015.pdf
http://www.interprogettied.com/tecnologie-alimentari-n2-marzo-2015/},
year = {2015},
date = {2015-03-01},
journal = {Tecnologie Alimentari},
volume = {2},
pages = {32-36},
abstract = {L’obiettivo primario dei processi di sanitizzazione e di trasformazione \`{e} quello di rendere gli alimenti conservabili nel tempo, edibili e pi\`{u} gustosi. Questo scopo non pu\`{o} per\`{o} essere disgiunto da fattori importanti quali il mantenimento del loro patrimonio nutritivo e la sostenibilit\`{a} di processo. Da ci\`{o} l’interesse verso tecnologie pi\`{u} efficaci e allo stesso tempo meno invasive, da applicare per ottenere prodotti alimentari di elevata qualit\`{a}. },
keywords = {Tecnagri},
pubstate = {published},
tppubtype = {article}
}
L’obiettivo primario dei processi di sanitizzazione e di trasformazione è quello di rendere gli alimenti conservabili nel tempo, edibili e più gustosi. Questo scopo non può però essere disgiunto da fattori importanti quali il mantenimento del loro patrimonio nutritivo e la sostenibilità di processo. Da ciò l’interesse verso tecnologie più efficaci e allo stesso tempo meno invasive, da applicare per ottenere prodotti alimentari di elevata qualità.
Cascone, Sara; Barba, Anna Angela; Lamberti, Gaetano; Marra, Francesco; Titomanlio, Giuseppe
Bioaccessibility of active principles: an in-vitro reproduction of human physiology Proceedings Article
In: Proccedings of 4th International Conference on Food Digestion, pp. 1–1, 4th International Conference on Food Digestion, Naples, Italy, 2015.
BibTeX | Tags: In vitro, Pharmacokinetics
@inproceedings{cascone2015b,
title = {Bioaccessibility of active principles: an in-vitro reproduction of human physiology},
author = { Sara Cascone and Anna Angela Barba and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio},
year = {2015},
date = {2015-03-01},
booktitle = {Proccedings of 4th International Conference on Food Digestion},
pages = {1--1},
publisher = {4th International Conference on Food Digestion},
address = {Naples, Italy},
keywords = {In vitro, Pharmacokinetics},
pubstate = {published},
tppubtype = {inproceedings}
}
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Modeling the Drug Release from Hydrogel-Based Matrices Journal Article
In: Molecular Pharmaceutics, vol. 12, no 2, pp. 474–483, 2015, ISSN: 1543-8384.
Links | BibTeX | Tags: Hydrogel Modeling
@article{Caccavo2015c,
title = {Modeling the Drug Release from Hydrogel-Based Matrices},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://pubs.acs.org/doi/abs/10.1021/mp500563n},
doi = {10.1021/mp500563n},
issn = {1543-8384},
year = {2015},
date = {2015-02-01},
journal = {Molecular Pharmaceutics},
volume = {12},
number = {2},
pages = {474--483},
publisher = {American Chemical Society},
chapter = {474},
keywords = {Hydrogel Modeling},
pubstate = {published},
tppubtype = {article}
}
Barba, Anna Angela; Lamberti, Gaetano; Sardo, Carla; Dapas, Barbara; Abrami, Michela; Grassi, Mario; Farra, Rossella; Tonon, F; Forte, Giancarlo; Musiani, F; Licciardi, M; Pozzato, G; Zanconati, F; Scaggiante, Bruna; Grassi, Gabriele; Cavallaro, Gennara
Novel Lipid and Polymeric Materials As Delivery Systems for Nucleic Acid Based Drugs. Journal Article
In: Current drug metabolism, vol. 16, no 6, pp. 427-452, 2015, ISSN: 1389-2002.
Abstract | Links | BibTeX | Tags: Biopolymer, Drug Delivery Systems, liposome, Micro and Nano Vectors, nucleic acid based drugs
@article{Barba2015,
title = {Novel Lipid and Polymeric Materials As Delivery Systems for Nucleic Acid Based Drugs.},
author = { Anna Angela Barba and Gaetano Lamberti and Carla Sardo and Barbara Dapas and Michela Abrami and Mario Grassi and Rossella Farra and F Tonon and Giancarlo Forte and F Musiani and M Licciardi and G Pozzato and F Zanconati and Bruna Scaggiante and Gabriele Grassi and Gennara Cavallaro},
url = {http://benthamscience.com/journals/current-drug-metabolism/article/133927/},
doi = {10.2174/1389200216666150812142557},
issn = {1389-2002},
year = {2015},
date = {2015-01-01},
journal = {Current drug metabolism},
volume = {16},
number = {6},
pages = {427-452},
abstract = {Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro-interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality.},
keywords = {Biopolymer, Drug Delivery Systems, liposome, Micro and Nano Vectors, nucleic acid based drugs},
pubstate = {published},
tppubtype = {article}
}
Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro-interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality.
Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Lamberti, Gaetano
Liposoluble vitamin encapsulation in shell–core microparticles produced by ultrasonic atomization and microwave stabilization Journal Article
In: LWT - Food Science and Technology, vol. 64, no 1, pp. 149–156, 2015, ISSN: 00236438.
Abstract | Links | BibTeX | Tags: drug delivery, Micro and Nano Vectors, Microwave drying, Shell{–}core microparticles, Ultrasonic energy, Vitamins
@article{Barba2015a,
title = {Liposoluble vitamin encapsulation in shell\textendashcore microparticles produced by ultrasonic atomization and microwave stabilization},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S002364381500403X},
doi = {10.1016/j.lwt.2015.05.040},
issn = {00236438},
year = {2015},
date = {2015-01-01},
journal = {LWT - Food Science and Technology},
volume = {64},
number = {1},
pages = {149--156},
abstract = {Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.},
keywords = {drug delivery, Micro and Nano Vectors, Microwave drying, Shell{\textendash}core microparticles, Ultrasonic energy, Vitamins},
pubstate = {published},
tppubtype = {article}
}
Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.