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Titolo
Identificazione di sistemi di rilascio ottimali per i Nucleic Acid Based Drugs e studio dei meccanismi di azione in alcuni modelli di patologie umane infiammatorie e tumorali
Coordinatore: Mario Grassi
Sommario
Per il carcinoma epatocellulare, l’adenocarcinoma prostatico, la restenosi coronarica, l’aneurisma dell’aorta addominale, le patologie infiammatorie croniche dell’intestino e del polmone, tutte patologie ad ampia diffusione, è urgente un significativo miglioramento dell’efficacia degli approcci terapeutici disponibili. L’uso dei farmaci basati sugli acidi nucleici (NABD), una nuova ed emergente classe di molecole, è considerato molto promettente. Tuttavia, una limitazione all’uso dei NABD dipende dalla mancanza di sistemi di rilascio ottimali in grado di minimizzare la degradazione dei NABD nei fluidi biologici e di permetterne un’azione mirata ai soli tessuti malati.
Scopo di questo progetto è di sviluppare nuovi sistemi di rilascio per i NABD, adeguati alle patologie considerate. Il problema verrà affrontato dal punto di vista ingegneristico, ma anche chimico-farmacetico e bio-medico. Parteciperanno al progetto nove gruppi Universitari con il supporto di diciassette gruppi di ricerca non universitari.
Unità di ricerca
Unità | Responsabile | Attività |
01. UNITS | Mario Grassi | Read More
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02. UNISA | Gaetano Lamberti | Read More
Le attività principali del progetto di ricerca consisteranno nel:
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03. UNIPV | Piersandro Pallavicini | Read More
Per individuare un’efficace terapia per il carcinoma epatocellulare, studieremo il rilascio di NABD, selezionati dall’Unità 01, per mezzo di nanovettori basati su nanoparticelle d’oro non simmetriche (asymmetric branched nanoparticles, ABN) e su nanoparticelle sferiche di magnetite (MNP). |
04. UNINA | Stefano Guido | Read More
L’attività sarà focalizzata sullo studio dell’interazione tra le cellule del sangue umano, in particolare dei globuli rossi, sia con le pareti dei vasi che con le micro/nano particelle sviluppate dalle altre Unità per il trasporto e il rilascio dei NABD. |
05. CNR NA | Domenico Larobina | Read More
L’obbiettivo è quello di fornire informazioni strutturali sui sistemi impiegati nel rilascio dei NABD proposti dalle altre Unità coinvolte nel progetto. A tal fine verranno utilizzate sia tecniche spettroscopiche che meccaniche. Tale caratterizzazione costituisce un indispensabile supporto conoscitivo necessario alla messa a punto dei dispositivi in grado di rilasciare i NABD. |
06. UNIPA1 | Gennara Cavallaro | Read More
Progetteremo sistemi di rilascio per i NABD utilizzabili nelle condizioni patologiche proposte dalle Unità 01, 02, 08; in particolare, valuteremo:
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07. UNIPA2 | Valerio Brucato | Read More
Prepareremo scaffolds polimerici (PLLA e/o mix PLLA/PLA) pre-angiogenizzati, come da brevetto proprietario, ed effettueremo test “in vitro” sul rilascio di NABD. |
08. UNIFG | Sante Di Gioia | Read More
Al fine di trovare nuovi approcci terapeutici dell’asma grave, proponiamo di usare NABD diretti contro GM-CSF, HMGB1, e TGF-ß1. In collaborazione con l’Unità 01 verranno selezionati i NABD appropriati; con il supporto Unità 02, 05 e 06 verranno sviluppati adeguati sistemi di rilascio.
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09. POLIMI | Davide Manca | Read More
Il nostro contributo consiste in un servizio di modellazione matematica per le Unità del presente progetto. La modellazione riguarderà due argomenti diversi:
Per entrambi gli obiettivi, di particolare utilità sarà il modello sviluppato dall’Unità 07 |
Prodotti della ricerca
Articoli pubblicati su riviste internazionali
Read More2017
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}
}
2016
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}
}
2015
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}
}
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}
}
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}
}
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
In: Materials Science and Engineering: C, vol. 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}
}
Lavori in atti di convegno internazionali
Read More2014
Caccavo, Diego; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications Proceedings Article
In: Proceedings of CHISA 2014, pp. 1–1, CHISA 2014, Prague, Czech Republic, 2014.
BibTeX | Tags: Hydrogel Characterization, Hydrogel Modeling
@inproceedings{d.2014,
title = {Testing and modelling of hydrogels behavior for pharmaceutical and biomedical applications},
author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
year = {2014},
date = {2014-08-01},
booktitle = {Proceedings of CHISA 2014},
pages = {1--1},
publisher = {CHISA 2014},
address = {Prague, Czech Republic},
keywords = {Hydrogel Characterization, Hydrogel Modeling},
pubstate = {published},
tppubtype = {inproceedings}
}
Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Titomanlio, Giuseppe; D'Amore, Matteo; Barba, Anna Angela
MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS Proceedings Article
In: 13th European Symposium on Controlled Drug Delivery, pp. 3–4, ESCDD 2014, Egmond aan Zee, The Netherlands, 2014.
BibTeX | Tags: Hydrogel Modeling
@inproceedings{s.2014,
title = {MODELING THE BEHAVIOR OF SWELLABLE HYDROGELS-BASED MATRICES FOR PHARMACEUTICAL APPLICATIONS},
author = { Sara Cascone and Diego Caccavo and Gaetano Lamberti and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},
year = {2014},
date = {2014-04-01},
booktitle = {13th European Symposium on Controlled Drug Delivery},
pages = {3--4},
publisher = {ESCDD 2014},
address = {Egmond aan Zee, The Netherlands},
keywords = {Hydrogel Modeling},
pubstate = {published},
tppubtype = {inproceedings}
}
Disseminazione
I meeting 5-6 febbraio 2013 – Trieste
Scarica la locandina: I meeting PRIN
II meeting 27-29 settembre 2013 – Palermo
Programma:
Scarica la locandina: II meeting PRIN
III meeting 20-21 giugno 2014 – Ustica
Scarica la locandina: III meeting PRIN
IV meeting 2-3 febbraio 2015 – Milano
Programma:
Scarica la locandina: IV meeting PRIN
V meeting 14-15 settembre 2015 – Salerno
Vai alla pagina dedicata: Workshop – Nuovi sviluppi della terapia genica
Programma:
Scarica la locandina: V meeting PRIN
VI meeting 24-25 Maggio 2016 – Trieste
Locandina e programma:
Scarica la locandina: VI meeting PRIN