Thermoreversible gelation of poly(ethylene glycol)/poly(ester anhydride) triblock copolymernanoparticles for injectable drug delivery systems

Abstract

The purpose of this study was to design injectable polymer formulations for controlled release of paclitaxel and Bovine serum albumin (BSA) using amphiphilic triblock copolymer (mPEG-b-P(OA-DLLA)-b-mPEG) consisting of methoxy poly(ethylene glycol) (mPEG), poly(octadecanedioic anhydride) (POA) and D,L-lactic acid oligomer (ODLLA). An aqueous dispersion of mPEG-b-P(OA-DLLA)-b-mPEG nanoparticle freeze-dried powder (NP-FDP) can undergo a sol–gel–sol transition as the temperature is increased from 4 to 90 °C. The critical gelation concentration (CGC) and lower critical transition temperature (LCTT) are decreased with the increase of P(OA-DLLA) block length in copolymers. During the in vitro degradation process, the content of mPEG in hydrogels slightly changed after the initial sharp reduction, which makes the average particle size in the degradation liquid increase. In vitro release studies demonstrate that there is no initial burst of drug from both hydrogel formulations containing paclitaxel (1 wt%) and BSA (1 wt%). The in vivo hydrogel formation and biocompatibility results confirm that the copolymer NP hydrogel is biocompatible and non-cytotoxic. Therefore, mPEG-b-P(OA-DLLA)-b-mPEG NP hydrogel is suitable for the controlled release of incorporated drugs for long durations.