pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane)

A series of novel pH- and temperature-responsive multiblock copolymers (poly(PEG/HEP urethane)) consisting of poly(ethylene glycol) (PEG) and poly(amino urethane) (PAU) were synthesized, and their physicochemical properties were studied. The amphiphilic block copolymers were synthesized from PEG, 1,4-bis(hydroxyethyl) piperazine (HEP) and 1,6-diisocyanato hexamethylene (HDI) in the presence of dibutyltin dilaurate as a catalyst. The resulting polymers were examined by FT-IR, H-1 and C-13 NMR spectroscopies and gel permeation chromatography (GPC). The solution properties of the copolymers were studied by turbidity measurement and fluorescence spectroscopy. The copolymers showed a pH-dependent soluble-insoluble transition in diluted aqueous solutions. The concentrated polymer solutions exhibited a thermo-induced sol-gel-sol phase transition at pH 6.8-7.4. The gel window covers the physiological conditions. After a subcutaneous injection of the multiblock copolymer solution into mice, a transparent and soft gel was formed immediately. The in vitro release of a model anticancer drug, chlorambucil, persisted over 2 weeks under physiological conditions. (C) 2008 Elsevier Ltd. All rights reserved.