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Polymeric Nanoparticles for Targeted Administration of Therapeutic Proteins

Federica Chiellini 1Vincenzina Caruso 1AnnaMaria Piras 2Tiziana Pizzi 1Roberto Solaro 1Bruno Fiorentino 2Emo Chiellini 1

1. University of Pisa - Dept. Chemistry & Ind. Chemistry (UNIPI), Via Risorgimento, 35, Pisa 56126, Italy
2. Kedrion SpA (Kedrion), Loc. Ai Conti 5, Castelvecchio Pascoli (Lucca) 55020, Italy

Abstract

In the last decades, the original uses of polymers in clinical medicine as essential components of permanent prosthetic devices are being replaced by the development of new strategies. Among the others, controlled drug delivery technology represents one of the most rapidly advancing areas of science in which polymer and pharmaceutical scientists are contributing to biomedical research field. The possibility of achieving time and space controlled release of drug is a main challenge that drives much of current innovation in biomaterials science. In particular, controlled release is strongly required for unconventional drugs such as proteins and oligopeptides. Moreover, if polymer surface modification is possible, a targeted delivery is achievable, resulting in enhancement of the therapeutic efficacy of the dosage forms and lowering the toxic effects. Particularly, the use of synthetic bioerodible polymers for the formulation of protein loaded nanospheres offers the advantage of a tailored design of release and bioerosion kinetics. In this respect, the present work aimed at reporting on a study for aimed at the formulation of nanoparticles loaded with a protein drug with catalytic activity. Copolymers of maleic anhydride with butyl vinyl ether converted into the corresponding amphihilic graft copolymer by hemiesterification with 2-methoxyethanol (VAM41) were prepared with molecular weight ranging from 300 to 30 kDa. Nanoparticles were prepared by mean of a proprietary method based on co-precipitation technique using a combination of the prepared synthetic polymers, human serum albumin, a steric stabilizer and trypsin as a model protein drug. A careful in vitro evaluation of synthetic polymers and nanoparticles cytotoxicity was carried out as well as investigation to assess the preservation of biological activity of trypsin loaded in nanoparticles.

 

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Presentation: oral at E-MRS Fall Meeting 2004, Symposium B, by Federica Chiellini
See On-line Journal of E-MRS Fall Meeting 2004

Submitted: 2004-04-29 16:31
Revised:   2009-06-08 12:55