Abstract
The purpose of this study is to understand the effect of copolymer composition on the drug delivery system. A series of biodegradable mPEG-PLGA diblock copolymers, [PLGA]/[mPEG] ratio from 1.46 to 3.01, were synthesized by ring-opening polymerization. Methoxy poly(ethylene glycol)(mPEG) of 350, 550 and 750, were used as the hydrophilic segment. Our results showed that copolymers of mPEG350 series and [PLGA]/[mPEG] at 3.01 were insoluble in water. The other copolymers in aqueous solution formed nanoparticles with critical micelle concentrations below 1×10-2 mg/ml. mPEG550 and mPEG750 series copolymers had thermosensitive properties with mPEG-PLGA(550-1405) having a wider gelation window. However, the gelation temperatures of mPEG750 series copolymers were above body temperature. Initially, hydrolysis occurred at the ester linkage of mPEG, which was followed by PLGA degradation occurring preferentially in GA unit rather than LA unit due to their hydrophobicity. Cytotoxicity and hemolysis test indicated that mPEG-PLGA diblock copolymers were biocompatible. Drug release study showed no initial burst and 15 wt% mPEG-PLGA(550-1405) hydrogel had the optimal drug release behavior. Before day9, drug release rate decreased as the concentration of copolymer aqueous solution increased. But this relationship inverted after day9. We inferred that this was due to the crystallization of degraded oligomer in the hydrogel. In vivo study showed that implantation of the mPEG-PLGA hydrogel containing Teicoplanin was effective in treating osteomyelitis in rabbits. The effect of copolymer composition on the drug delivery system was elucidated in this study. The use of mPEG-PLGA-based biodegradable hydrogels may hold great promise as a therapeutic strategy for osteomyelitis.