Charge modified, comb-like graft-polyesters for drug delivery and DNA vaccination: Synthesis and Characterization of Poly(vinyl dialkylaminoalkylcarbamate-co-vinyl acetate-co-vinyl alcohol)-graft-poly(D,L-lactide-co-glycolide)s

In the present thesis a novel tailor-made polyester class based on amine-modified backbones and PLGA side chains was synthesized after designing its chemical structure under consideration of all necessary assumptions for a drug delivery system. Varying side chain length and amine...

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Bibliographic Details
Main Author: Wittmar, Matthias
Contributors: Kissel, Thomas (Prof. Dr.) (Thesis advisor)
Format: Dissertation
Language:English
Published: Philipps-Universität Marburg 2004
Pharmazeutische Technologie und Biopharmazie
Subjects:
DNS
Pol
Online Access:PDF Full Text
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Summary:In the present thesis a novel tailor-made polyester class based on amine-modified backbones and PLGA side chains was synthesized after designing its chemical structure under consideration of all necessary assumptions for a drug delivery system. Varying side chain length and amine substitution these polyesters can be especially designed for drug delivery problems. Their structure was clarified by NMR-spectroscopy and GPC-MALLS (multi-angle-laser-light-scattering). By variation of side chain length and /or amine substitution the solution and thermal behavior could be adjusted. Aimed amine substitution could be used to control degradation speed of the polyesters. Grafting of short side chain onto amine modified PVA converted a pure bulk erosion into a mixed surface and bulk erosion. To our knowledge this is the first time a degradation time of PLGA polyesters smaller than 15 days could be reached and could be freely modified by changing side chain length and amine substitution. Due to their solution and thermal behavior this polymer class is suitable for manufacturing of microparticles and implants. Using two dimensional NMR techniques like 1H-1H COSY, 1H-13C HMBC and 1H-13C HMQC a clear assignment of 1H and 13C NMR signals of the amine modified PVAs was established. The microstructure of the PVA backbones was investigated. It was demonstrated that some of the synthesized Polyesters have interesting transfection abilities in in-vitro experiments on L929 mouse fibroblasts. Especially, the particles formed by P(68)-10 feature an extraordinary high transfection even higher than that of PEI/DNA complexes. Holding the side chain length constant it was possible to increase transfection by increasing the amine substitution of the backbone. An opposite effect results at constant amine substitution and elongation of the PLGA chains.
Physical Description:113 Pages
DOI:https://doi.org/10.17192/z2004.0075