多指标综合评价法优选阿霉素微球的制备工艺及体内的初步考察

 目的优化阿霉素微乳-羟基乙酸共聚物(PLGA)微球制备工艺。方法采用“复乳-液中干燥”法制备阿霉素PLGA微球。通过正交实验结合多指标综合评价法优选最佳制备工艺。并通过测定大鼠皮下注射微球残留药量对优化制备工艺制备的微球进行初步的体内释放研究。结果通过对正交实验Z值结果进行分析,最佳制备工艺为:PLGA质量浓度为800 g·L^-1,W/O相体积之比为1∶3,PVA质量浓度为4%。阿霉素PLGA微球在大鼠体内释放平稳,突释较小,10 d的残留药量为24.1%。结论正交实验结合多指标综合评价法用于载药微球的制备工艺优化实用有效。阿霉素PLGA微球能达到治疗肿瘤的长效释药的要求。

Optimization of Preparation Condition of Adriamycin PLGA Microspheres by Multi- index Evaluations and Preliminary Study on Their Release Behavior in Rats

OBJECTIVE To optimize the preparation conditions of adriamycin PLGA microspheres.METHOD Adriamycin PLGA microspheres were prepared by double emulsion method.The optimum preparation conditions were selected with orthogonal design combined with multi-index test.Then their release behavior in vivo was investigated by measuring residual dosage after subcutaneous injection in rats.RESULTS According to Z-score results,the optimum preparation conditions of adriamycin PLGA microspheres was: PLGA concentration 800 g·L^-1,W/O volume ratio 1:3,PVA concentration 4%.The release curve of adriamycin PLGA microspheres in rats was smooth.Initial burst release was very small.The residual dosage in 10 d after subcutaneous injection in rats was 24.1%.CONCLSION Orthogonal design combined with multi-index test can be used to represent the most desirable variables in the preparation of drug-loaded microspheres.Adriamycin PLGA microspheres can reach sustained-releasing requirement for treating tumors.