Polyacetal and poly(ortho ester)–poly(ethylene glycol) graft copolymer thermogels: Preparation, hydrolysis and FITC-BSA release studies

Graft copolymers comprised of a polyacetal backbone with pendant poly(ethylene glycol) side-chains were prepared using a condensation reaction between a divinyl ethers, a diol and Fmoc-protected serinol, followed by deprotecting the amine and reacting the polyacetal with pendant amino groups with PE...

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Bibliographic Details
Published in:	Journal of controlled release Vol. 116; no. 2; pp. 219 - 225
Main Authors:	Schacht, Etienne, Toncheva, Veska, Vandertaelen, Kristin, Heller, Jorge
Format:	Journal Article Conference Proceeding
Language:	English
Published:	Amsterdam Elsevier B.V 28-11-2006 Elsevier
Subjects:	Acetals - chemistry Biological and medical sciences Chromatography, Gel Delayed-Action Preparations Drug Carriers - chemical synthesis Drug release Erosion-controlled FITC-BSA Fluorescein-5-isothiocyanate - analogs & derivatives Fluorescein-5-isothiocyanate - chemistry Fluorescent Dyes - chemistry Gels General pharmacology Graft copolymer Hydrogen-Ion Concentration Hydrolysis Medical sciences Molecular Weight Pharmaceutical technology. Pharmaceutical industry Pharmacology. Drug treatments Poly(ortho ester) Polyacetal Polyethylene Glycols - chemistry Polymers - chemistry Rheology Serum Albumin, Bovine - chemistry Solubility Temperature Thermogel Time Factors Viscosity Drug release FITC-BSA Polyacetal Erosion-controlled Graft copolymer Poly(ortho ester) Thermogel Drug Pharmaceutical technology Hydrolysis Ester Preparation Glycol Release Erosion
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Summary:	Graft copolymers comprised of a polyacetal backbone with pendant poly(ethylene glycol) side-chains were prepared using a condensation reaction between a divinyl ethers, a diol and Fmoc-protected serinol, followed by deprotecting the amine and reacting the polyacetal with pendant amino groups with PEG-α-methoxy-ω-succimidylcarbonate. A series of materials having lower critical solution temperature (LCST) between 25 and 60 °C has been prepared. Since LCST is determined by the hydrophilic–hydrophobic balance, and this in turn is determined by the molecular weight of the polyacetal backbone, the molecular weight of the grafted PEG and the amount grafted, materials having a desired LCST could be readily prepared. Incorporating FITC-BSA at 1 wt.% into the thermogel resulted in sustained release over about 100 days at pH 7.4 and 40 days at pH 5.5 without a burst and by reasonably linear kinetics. Incorporating FITC-BSA at 5 wt.% into the thermogel significantly increased delivery time at pH 5.5 and decreased the difference in delivery rates between pH 5.5 and pH 7.4. FITC-BSA is released by a predominantly erosion-controlled process and FITC-BSA depletion coincides closely with total gel dissolution. More rapidly eroding thermogels were prepared by replacing the polyacetal backbone with a poly(ortho ester) backbone. Such gels completely dissolved between 3 and 6 days. It is hoped that intermediate erosion rates can be achieved by preparing backbones containing both acetal and ortho ester linkages. Such materials have been prepared and shown to have LCST values in the desired range, but no erosion, or drug release studies have as yet been completed.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0168-3659 1873-4995
DOI:	10.1016/j.jconrel.2006.07.026