多西紫杉醇白蛋白微球的制备及性质

Preparation and properties of docetaxel-loaded albumin microspheres

目的制备多西紫杉醇白蛋白微球,并对处方工艺进行优化,考察其体外释放。方法采用改进的乳化-化学交联法制备多西紫杉醇白蛋白微球,通过正交设计实验考察药质比、交联剂的加入量、交联时间、转速等因素,以微球的载药量和包封率为指标进行综合评分,优选出最佳制备工艺。扫描电镜观察微球形态,HPLC法测定微球包封率及载药量;以累积释药百分率为指标,通过方程拟合释药曲线,考察制剂的体外释药特性。结果优化处方制得的微球在扫描电镜下为类球形,平均粒径为35.48μm,包封率为(61.35±3.12)%,载药量为(5.25±0.41)%,制剂48 h体外累积释药百分率为88.9%,体外释放符合Higuchi方程Q=14.205t1/2+0.35(r=0.991 6)。结论本实验获得了较理想的多西紫杉醇白蛋白微球,其体外释放特性符合缓释制剂特征。

Objective To prepare bovine serum albumin microspheres containing docetaxel(DT-BSA-MS), to optimize the formulation by orthogonal experiment design, and evaluate its in vitro release behavior. Methods Microspheres were prepared by modified emulsification chemical cross-linking method. Preparation process was optimized by orthogonal experiment design and the drug:polymer ratio, the amount of cross-linking agent, duration of cross-linking and stirring speed were investigated. Selected formulations were characterized in terms of entrapment efficiency and drug content. The morphology of the MS was observed by SEM. The encapsulation efficiency and drug-loading of the MS were examined by HPLC method. The in vitro release was investigated, based on accumulated release and the fitting of release curve. Results The optimized results show that DT-BSA-MS were spherical with an average diameter of 35.48 μm, drug-loading content of(5.25±0.41)%, encapsulation efficiency of(61.35±3.12)%, and accumulated release of 88.9% at 48 h, and the in vitro release was in line with Higuchi equation Q = 14.205t1/2 + 0.35(r=0.991 6). Conclusions Using this formulation and preparation method, ideal docetaxel albumin microspheres were obtained, and the in vitro release characteristics satisfied the requirement of sustained-released preparation.