Drug release and biocompatibility of self-assembled micelles prepared from poly (ɛ-caprolactone/glycolide)-poly (ethylene glycol) block copolymers

Abstract

A series of poly(e-caprolactone/glycolide)-poly(ethylene glycol) (P(CL/GA)-PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of e-caprolactone and glycolide using mPEG as macro-initiator and stannous octoate as catalyst. Self-assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(epsilon-caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)-PEG micelles are promising for prolonged release of hydrophobic drugs.