PH/temperature sensitive poly(ethylene glycol)-based biodegradable polyester block copolymer hydrogels

Novel pH and temperature sensitive biodegradable block copolymers composed of poly(ethylene glycol) (PEG), polyglycolide (GA), F.-caprolactone (CL) and sulfamethazine oligomers (OSMs) were synthesized by ring opening polymerization and 1,3-dicyclohexyl-carbodiimide (DCC) mediated coupling reactions. Their physicochemical properties in aqueous media were characterized by H-1 NMR spectroscopy and gel permeation spectroscopy. The sol-gel phase transition behavior of OSM-PCGA-PEG-PCGA-OSM block copolymers was investigated both in solution and injection to PBS buffer at pH 7.4 and 37 degrees C. Aqueous solutions of OSM-PCGA-PEG-PCGA-OSM changed from a sol to a gel phase with increasing temperature and decreasing pH. The sol-gel transition properties of these block copolymers are influenced by the hydrophobic/hydrophilic balance of the copolymers, block length, hydrophobicity, stereoregularity of the hydrophobic components within the block copolymer, and the ionization of the pH functional groups in the copolymer, which depends on the environmental pH. Degradation of the triblock and pentablock copolymers at 37 degrees C (pH 7.4), and at 0 degrees C and 5 degrees C both at pH 8.0, was investigated. It was demonstrated here using the in vitro test method, that the anticancer agent paclitaxel (PTX) could be loaded and released by the pH and temperature sensitive OSM-PCGA-PEG-PCGA-OSM block copolymer, such that this could be used as a suitable matrix for subcutaneous injection in drug delivery systems. (c) 2006 Elsevier Ltd. All rights reserved.