Preparation and Evaluation of pH-Sensitive Paclitaxel-loaded Copolymeric Micelles / 中国药师

ABSTRACT

Objective:To synthesize poly (2-ethyl-2-oxazoline)-poly(lactic acid) copolymer (PEOz-PLA), prepare pH-sensitive paclitaxel-loaded polymeric micelles, and evaluate the in vitro properties. Methods: The structures of all the synthesized copolymers were confirmed by 1 HNMR and Fourier transform infrared spectroscopy ( FTIR) . The drug-loaded micelles were prepared by a dialysis method. The micelles solution was freeze-dried and the lyoprotectants were screened. The critical micelle concentrations ( CMC) of the copolymers were measured by pyrene fluorescent probe technique. The distribution of particle size was measured by dynamic light scat-tering ( DLS) . The in vitro release behavior of the loaded micelles at different pH conditions was studied by a dialysis method. Re-sults:The CMC of micelles was 25. 63 mg·ml-1 . When 10% polyethylene glycol 4000 was used as the lyoprotectant, the re-solubili-ty of micelles was good and the distribution of particle size was narrow. The drug loading rate of micelles was 8. 12% and the encapsu-lation efficiency was 69. 33%. The average particle size of freeze-dried micelles was 183. 7 nm. The in vitro release of the drug-loaded micelles showed that the drug released slowly at pH 7. 4 and fast at pH 5. 0, which indicated that the change of pH could affect the drug release. Conclusion:The preparation of PEOz-PLA polymer micelles is simple. The particle size, entrapment efficiency and drug loading are controllable. The micelles have a certain sustained-release effect, which provides basis for further pharmacological study and clinical application.