(The) synthesis and sol-gel transition behavior of the biodegradable comb-like PEG-PLGA block copolymer

Abstract

Biodegradable amphiphilic copolymers having stimuli-sensitivity with potential application as the drug carrier were synthesized. The effect of the structure and composition of the copolymer on micellization and sol-gel transition behavior was analyzed. Copolymer was prepared by reacting PEG-PLGA amiphiphilic block copolymer with NIPAAm which had LCST behavior at 32℃, or with polyacrylamide which showed pH sensitivity. Synthesized multi-branched copolymer showed temperature or temperature/pH sensitivity according to backbone material. First copolymer was synthesized by free radical polymerization of (PLGA-b-PEG)MA macromonomer and N-isopropylacrylamide(NIPAAm). Macromonomer was prepared by ring opening polymerization of DL-lactide/Glycolide on hydrophilic poly(ethylene glycol)monomethacrylate(PEGMA). Copolymers of various compositions were synthesized by changing the feed ratio of monomers to investigate the effect of the structure and composition of the copolymer on properties. Molecular weights and chemical structures were confirmed by GPC and 1H-NMR. The composition of NIPAAm in the copolymer was higher than the feed composition due to the bulkiness of (PEG-PLGA)MA macromonomer. Sol-gel transition and micellization behavior were examined by the tube-tilting method and UV measurement, respectively. The sol region in the aqueous solution and the critical micelle concentration(CMC) increased with increasing the NIPAAm content of copolymer. The sol-gel transition showed deviation and the micelle size decreased abruptly at 32℃ due to the change of hydrophilic to hydrophobic nature in the NIPAAm chain at LCST. Second copolymer of polyacrylamide-g-poly(PEG-b-PLGA) was synthesized by coupling of NHS activated PEG-PLGA block and amide group of AAm oligomer(Mn=1500). For Two different kinds of PEG-b-PLGA block copolymers were prepared by changing the feed ratio of LA : GA. Feed ratio of amphiphilic block to oligomer also varied to change the number of grafted br...