Sixteen millions of people are diabetics in the United States. Finding an oral way to deliver the insulin they need would improve the quality of their life. For this purpose biodegradable and biocompatible nanovesicles encapsulating some insulin have been synthesized. Those nanovesicles are made by self-assembly of a triblock copolymer poly(ethylene glycol)-bpoly( lactic acid)-b-poly(glutamic acid) (PEG-b-PLA-b-PGlu). The triblock copolymer has been prepared in several steps by multi-step anionic ringopening polymerization. The first step consisted in the preparation of the diblock copolymer PEG-b-PLA. This diblock copolymer was synthesized by ring opening of racemic lactide, using a zinc alkoxide as an initiator. The second step was the synthesis of the poly(glutamic acid). The polybenzyl(glutamic acid) was obtained by ring opening polymerization of the N-Carboxyanhydride of the corresponding amino acid. Finally, the benzyl group was deprotected via protonolysis, to generate the homopolymer. This triblock was successfully obtained by coupling a diblock copolymer PEG-bxv PLA and a homopolymer poly(glutamic acid). In the presence of an aqueous solution of insulin where the pH is between 7 and 9, the triblock copolymer self-assembles in nanovesicles containing a part of the free insulin. In the intestine, the vesicles are highly solvated due to the deprotonnated poly(glutamic acid) hair which are expected to be located on the outside. Moreover, to resist from the gastric acidity, the nanovesicles are protected with gastro resistant polymer, Eudragit, which stay solid at acidic pH but get dissolved in the intestine (where the pH is slightly basic), releasing the vesicles. All the polymers have been characterized using 1H NMR and GPC. The percentage of encapsulation of insulin has been measured by HPLC some in-vivo experiments have been done on Sprague-Dawley rats.
Identifer | oai:union.ndltd.org:CCSD/oai:tel.archives-ouvertes.fr:tel-00359278 |
Date | 12 August 2005 |
Creators | Collette, Floraine |
Source Sets | CCSD theses-EN-ligne, France |
Language | English |
Detected Language | English |
Type | PhD thesis |
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