藤黄酸B聚乙二醇单甲醚化脂质体的制备及大鼠体内药动学的研究  

Study on preparation and in vivo pharmacokinetics in rats of morellic acid B mPEG liposome

作　　者：吴培云[1] 李国转 姚亮[1] 贾步云 李睿[1] 陈卫东[1] 彭代银[1] 

机构地区：[1]安徽中医药大学药学院,安徽合肥230012

出　　处：《中草药》2017年第8期1553-1560,共8页Chinese Traditional and Herbal Drugs

基　　金：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)

摘　　要：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t1/2β为66.925 min,是MAB的4.43倍,是MAB-LPS的3.29倍;AUC0~∞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AUC0~∞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 MABmPEG-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 t1/2β 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; AUC0-∞ 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 AUC0-∞ of MAB in rats.

关 键 词：藤黄酸B 聚乙二醇单甲醚化脂质体 正交试验 体外释放 药动学 包封率 稳定性 透析法 缓释 长效 

分 类 号：R283.6[医药卫生—中药学]