目的 优化藤黄酸B（morellic acid B，MAB）聚乙二醇单甲醚（mPEG）化脂质体（MAB-mPEG-LPS）的制备工艺，并对其体外释放及大鼠体内药动学行为进行研究。方法 建立藤黄酸B定量分析方法，以包封率、粒径分布作为考察指标，采用正交试验设计优化MAB-mPEG-LPS处方，得到MAB-mPEG-LPS包封率最高的制备工艺；采用透射电镜下观察MAB-mPEG-LPS表面形态，考察MAB-mPEG-LPS在60 d内的稳定性，采用透析法对MAB-mPEG-LPS体外释放行为进行研究，雄性SD大鼠尾静脉分别注射1.50 mg/kg的MAB、MAB脂质体（MAB-LPS）、MAB-mPEG-LPS，比较MAB、MAB-LPS、MAB-mPEG-LPS药动学行为。结果 正交试验优化后MAB-mPEG-LPS的最优处方为氢化大豆卵磷脂（HSPC）128 mg，mPEG的用量为10 mg，HSPC-胆固醇（CH）质量比8：1，MAB-mPEG-LPS包封率达到83.21%，MAB-mPEG-LPS外观表面光滑，粒径均匀；体外释放结果表明MAB-mPEG-LPS具有缓释且长效作用，在60 d内储存稳定；MAB-mPEG-LPS中MAB在大鼠体内t_1/2β为66.925 min，是MAB的4.43倍，是MAB-LPS的3.29倍；AUC_0~∞为241.372 mg·min/L，是MAB在大鼠体内3.64倍，是MAB-LPS的1.99倍。结论 MAB-mPEG-LPS可延长MAB在大鼠体内的循环时间，增加体内AUC_0~∞等特性。

Objective To optimize the preparation process of morellic acid B (MAB) mPEG liposomes (MAB-mPEG-LPS), and to study the in vitro release behavior and pharmacokinetics of MAB-mPEG-LPS in rats. Methods The analytical method of MAB was established; Encapsulation efficiency and particle size were used as the indexes to optimize the mPEG liposomes by orthogonal test, and the highest encapsulation efficiency of MAB-mPEG-LPS was obtained; Transmission electron microscope was used to observe the surface morphology of MAB-mPEG-LPS, and the stability of MAB-mPEG-LPS was measured in 60 d. Dialysis method was also adopted to study the MAB-mPEG-LPS release in vitro; Male SD rats were injected with MAB (1.50 mg/kg), MAB-LPS (1.50 mg/kg), MAB-mPEG-LPS (1.50 mg/kg) via tail vein, and differences in pharmacokinetics parameters of MAB, MAB-LPS, and MAB- mPEG-LPS were compared. Results The optimized formula of MAB-mPEG-LPS: HSPC was 128 mg, mPEG was 10 mg, HSPC-CHOL was 8:1. Encapsulation efficiency of MAB-mPEG-LPS was 83.21%. MAB-mPEG-LPS had uniform particle size and smooth surface; In vitro release results showed that the MAB-mPEG-LPS had slow release and long-term effect. It was stable in 60 d; In vivo study showed that t_1/2β of MAB in MAB-mPEG-LPS was 66.925 min, which was 4.43 fold to MAB. MAB-mPEG-LPS was 3.29 fold to MA-LPS; AUC_0-∞ of MAB in MAB-mPEG-LPS was 241.372 mg·min/L, which was 3.64 fold to MAB. MAB-mPEG-LPS was 1.99 fold to MAB-LPS. Conclusion MAB-mPEG-LPS could prolong the circulation time and increase AUC_0-∞ of MAB in rats.

国家“重大新药创制”科技重大专项（2009ZX09103-399）；国家自然科学基金面上项目（81473387）；国家中医药管理局中药标准化项目（国中医药办科技函[2016]154号）；安徽省科技攻关计划项目（1301042099）