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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2016 |
Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano Modeling capillary formation in calcium and copper alginate gels Journal Article Materials Science and Engineering: C, 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. |
2014 |
Barba, Anna Angela; Lamberti, Gaetano; Rabbia, Luca; Grassi, Mario; Larobina, Domenico; Grassi, Gabriele Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications Journal Article Materials Science and Engineering: C, 37 , pp. 327–331, 2014, ISSN: 09284931. Abstract | Links | BibTeX | Tags: Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation @article{Barba2014b, title = {Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications}, author = { Anna Angela Barba and Gaetano Lamberti and Luca Rabbia and Mario Grassi and Domenico Larobina and Gabriele Grassi}, url = {http://www.sciencedirect.com/science/article/pii/S0928493114000423}, doi = {10.1016/j.msec.2014.01.034}, issn = {09284931}, year = {2014}, date = {2014-01-01}, journal = {Materials Science and Engineering: C}, volume = {37}, pages = {327--331}, abstract = {In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends.}, keywords = {Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation}, pubstate = {published}, tppubtype = {article} } In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends. |
Conference Proceedings
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2016 |
Caccavo, Diego; Ström, Anna; Larsson, Anette; Lamberti, Gaetano Modeling capillary formation in calcium and copper alginate gels Journal Article Materials Science and Engineering: C, 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. |
2014 |
Barba, Anna Angela; Lamberti, Gaetano; Rabbia, Luca; Grassi, Mario; Larobina, Domenico; Grassi, Gabriele Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications Journal Article Materials Science and Engineering: C, 37 , pp. 327–331, 2014, ISSN: 09284931. Abstract | Links | BibTeX | Tags: Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation @article{Barba2014b, title = {Modeling of the reticulation kinetics of alginate/pluronic blends for biomedical applications}, author = { Anna Angela Barba and Gaetano Lamberti and Luca Rabbia and Mario Grassi and Domenico Larobina and Gabriele Grassi}, url = {http://www.sciencedirect.com/science/article/pii/S0928493114000423}, doi = {10.1016/j.msec.2014.01.034}, issn = {09284931}, year = {2014}, date = {2014-01-01}, journal = {Materials Science and Engineering: C}, volume = {37}, pages = {327--331}, abstract = {In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends.}, keywords = {Alginate, Hydrogel Modeling, Modeling, Pluronic, Reticulation}, pubstate = {published}, tppubtype = {article} } In this work, blends of alginate/pluronic (F127) for biomedical applications were investigated. In particular, the kinetics of alginate chain reticulation by bivalent cations was studied by experimental and modeling approaches. Two kinds of sodium alginate were tested to obtain hard gel films. The thicknesses of the reticulated alginate films were measured as function of the exposure time and of the reticulating copper (Cu2+) solution concentration. The kinetics was described by a proper model able to reproduce the experimental data. The model parameters, evaluated based on the measurements of thicknesses as function of Cu2+ concentration and exposure time, were further validated by comparing the prediction of the model with another set of independent measurement; here, the depletion of Cu2+ ions in the conditioning solution above the reacting gel is measured as function of time. The tuned model could be used in the description of the future applications of the blends. |
Dissemination
I meeting 5-6 February 2013 – Trieste
Program:
Download the flier: I meeting PRIN
II meeting 27-29 September 2013 – Palermo
Program:
Download the flier: II meeting PRIN
III meeting 20-21 June 2014 – Ustica
Program:
Download the flier: III meeting PRIN
IV meeting 2-3 February 2015 – Milano
Program:
Download the flier: IV meeting PRIN
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
Flyer and program:
Download the flier: VI meeting PRIN