PRIN 2010-11(cod. 20109PLMH2) |
Title
Identification of optimal delivery systems for the Nucleic Acid Based Drugs and study of the action mechanisms in some models of human tumoral and inflammatory pathologies
Principal Investigator: Mario Grassi
Abstract
For hepatocellular carcinoma, prostate adenocarcinoma, coronary restenosis, abdominal aortic aneurism, inflammatory bowel and lung diseases, a significant improvement in the efficacies of the therapeutic approaches so far available is urgently required. The use of “nucleic acid based drugs” (NABDs), a novel and emergent class of molecules, is considered very promising. However, a limitation in NABD use as drugs depends on the lack of optimal delivery systems able to minimize NABD degradation in the biological fluid and allow the targeting to the diseased tissue.
The aim of this project is to develop novel delivery systems for NABDs, appropriate for the considered human pathologies. Our approach will take into consideration the different problematics related to the engineering field, but also chemical, pharmaceutical and biomedical filed. Nine University groups will take part to the project together with eigtheen other non-University research groups.
Research units
Unit | Team manager | Activities |
01. UNITS | Mario Grassi | Read More
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02. UNISA | Gaetano Lamberti | Read More
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03. UNIPV | Piersandro Pallavicini | Read More
To individuate an efficient therapy for hepatocellular carcinoma we will study the delivery NABDs, developed by Unit 01, by means of nanovectors based on gold asymmetric branched nanoparticles (ABN) and on spherical magnetite nanoparticles (MNP). |
04. UNINA | Stefano Guido | Read More
The activity is focused on the study of the interaction between human blood cells, in particular red blood cells, and either vessel walls or micro/nano particles, developed by the other Unit, for NABD delivery. |
05. CNR NA | Domenico Larobina | Read More
The aim is to support the other research units involved in the project with appropriate structural information on the gel systems employed in the release of NABD. For this specific purpose, we will adopt both mechanical and spectroscopic techniques. Such characterizations represent a useful support to set up the specific polymeric device able to release NABDs. |
06. UNIPA1 | Gennara Cavallaro | Read More
We will produce and characterize NABD delivery systems appropriate for the pathological conditions proposed by Units 01, 02 and 08; in particular we will evaluate:
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07. UNIPA2 | Valerio Brucato | Read More
We will prepare polymeric scaffolds (made of PLLA and/or PLLA/PLA mixtures) pre-angiogenized as from proprietary patent, and will carry out advanced “in vitro” tests on the NABD release. PLLA scaffold, featuring a pseudo-vascular structure, prepared as for the proprietary patent, will be cultured with mixed population of mesenchymal cells (to promote the ECM formation) and tumoral cells (of interest for the pathologies of this project) showing different metastatic strenght to generate structure close to a tumoral mass. By the “pseudo-vascular” system an “in vitro” evaluation of the performance shown by the specific NABDs dose release on tumoral mass will be evaluated. |
08. UNIFG | Sante Di Gioia | Read More
In order to tackle the limits of available therapeutic approaches in severe asthma, we plan to use NABDs targeting GM-CSF, HMGB1, and TGF-ß1. In collaboration with Unit I appropriate NABDs will be selected; with support of Units 02, 05 and 06 adequate delivery systems will be developed. |
09. POLIMI | Davide Manca | Read More
Our contribution consists of the modelling service for the other research Units. The modeling will be devoted to two different topics:
For both topics, a relevant model will be the one developed by Unit 07 |
Research products
Articles published on international journals
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2015 |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article International journal of pharmaceutics, 486 (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. |
2014 |
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis Journal Article Carbohydrate Polymers, 103 , pp. 348–354, 2014, ISSN: 01448617. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogels, Texture analysis, Water content @article{Cascone2014, title = {Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis}, author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861713012757}, doi = {10.1016/j.carbpol.2013.12.060}, issn = {01448617}, year = {2014}, date = {2014-03-01}, journal = {Carbohydrate Polymers}, volume = {103}, pages = {348--354}, abstract = {The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force\textendashpenetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.}, keywords = {Hydrogel Characterization, Hydrogels, Texture analysis, Water content}, pubstate = {published}, tppubtype = {article} } The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force–penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices. |
2013 |
Lamberti, Gaetano; Cascone, Sara; Cafaro, Maria Margherita; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis. Journal Article Carbohydrate polymers, 92 (1), pp. 765–8, 2013, ISSN: 1879-1344. Abstract | Links | BibTeX | Tags: HPMC, Hydrogel Characterization, Texture analysis, Water content @article{Lamberti2013a, title = {Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.}, author = { Gaetano Lamberti and Sara Cascone and Maria Margherita Cafaro and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861712010193}, doi = {10.1016/j.carbpol.2012.10.003}, issn = {1879-1344}, year = {2013}, date = {2013-01-01}, journal = {Carbohydrate polymers}, volume = {92}, number = {1}, pages = {765--8}, abstract = {In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.}, keywords = {HPMC, Hydrogel Characterization, Texture analysis, Water content}, pubstate = {published}, tppubtype = {article} } In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms. |
Conference Proceedings
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2015 |
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela Controlled drug release from hydrogel-based matrices: Experiments and modeling. Journal Article International journal of pharmaceutics, 486 (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. |
2014 |
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis Journal Article Carbohydrate Polymers, 103 , pp. 348–354, 2014, ISSN: 01448617. Abstract | Links | BibTeX | Tags: Hydrogel Characterization, Hydrogels, Texture analysis, Water content @article{Cascone2014, title = {Measurements of non-uniform water content in hydroxypropyl-methyl-cellulose based matrices via texture analysis}, author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861713012757}, doi = {10.1016/j.carbpol.2013.12.060}, issn = {01448617}, year = {2014}, date = {2014-03-01}, journal = {Carbohydrate Polymers}, volume = {103}, pages = {348--354}, abstract = {The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force\textendashpenetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices.}, keywords = {Hydrogel Characterization, Hydrogels, Texture analysis, Water content}, pubstate = {published}, tppubtype = {article} } The use of hydrogels in the preparation of controlled release pharmaceutical forms is extensively diffused. The main feature of these polymers is their ability to swell forming a gel layer when they enter in contact with fluids. Once the gel layer is formed, the drug contained in the matrix can easily diffuse ensuring a controlled release from the tablet. Measurement of water content within a hydrating matrix based on hydrogels is a key topic in the study of pharmaceutical solid dosage forms. The aim of this work is to evaluate the water content of swollen matrices composed by HPMC and theophylline both in axial and in radial direction, as a function of time, using a texture analysis. A relationship between water content and slope of the force–penetration curves has been obtained using a simplified system in which the water uptake is allowed only in radial direction, obtaining thus partially hydrated matrices with the water content varying only along the radial direction. Once the relationship has been validated, it has been applied in a more complex system in which the polymer swelling takes place in both axial and radial direction. Thus, using the texture analysis it has been possible to determine the water in each position within the hydrated matrices. |
2013 |
Lamberti, Gaetano; Cascone, Sara; Cafaro, Maria Margherita; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis. Journal Article Carbohydrate polymers, 92 (1), pp. 765–8, 2013, ISSN: 1879-1344. Abstract | Links | BibTeX | Tags: HPMC, Hydrogel Characterization, Texture analysis, Water content @article{Lamberti2013a, title = {Measurements of water content in hydroxypropyl-methyl-cellulose based hydrogels via texture analysis.}, author = { Gaetano Lamberti and Sara Cascone and Maria Margherita Cafaro and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba}, url = {http://www.sciencedirect.com/science/article/pii/S0144861712010193}, doi = {10.1016/j.carbpol.2012.10.003}, issn = {1879-1344}, year = {2013}, date = {2013-01-01}, journal = {Carbohydrate polymers}, volume = {92}, number = {1}, pages = {765--8}, abstract = {In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms.}, keywords = {HPMC, Hydrogel Characterization, Texture analysis, Water content}, pubstate = {published}, tppubtype = {article} } In this work, a fast and accurate method to evaluate the water content in a cellulose derivative-based matrix subjected to controlled hydration was proposed and tuned. The method is based on the evaluation of the work of penetration required in the needle compression test. The work of penetration was successfully related to the hydrogel water content, assayed by a gravimetric technique. Moreover, a fitting model was proposed to correlate the two variables (the water content and the work of penetration). The availability of a reliable tool is useful both in the quantification of the water uptake phenomena, both in the management of the testing processes of novel pharmaceutical solid dosage forms. |
Dissemination
I meeting 5-6 February 2013 – Trieste
Program:
Download the flier: I meeting PRIN
II meeting 27-29 September 2013 – Palermo
Program:
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III meeting 20-21 June 2014 – Ustica
Program:
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IV meeting 2-3 February 2015 – Milano
Program:
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V meeting 14-15 September 2015 – Salerno
Go to the dedicated page: Workshop – New trends in gene therapy
Program:
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VI meeting 24-25 May 2016 – Trieste
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