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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| Format: | Dissertation |
| Sprache: | Englisch |
| Veröffentlicht: |
Philipps-Universität Marburg
2004
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| Zusammenfassung: | 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. |
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| Umfang: | 113 Seiten |
| DOI: | 10.17192/z2004.0075 |