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目的优化藤黄酸长循环脂质体制备工艺,并对其体外释放及体内药动学进行研究。方法建立藤黄酸定量测定方法;以藤黄酸包封率作为考察指标,采用Box-Behnken试验设计优化脂质体组方,得到藤黄酸包封率最高的处方;采用电镜扫描观察藤黄酸脂质体表面形态,采用透析法对脂质体体外释放进行研究,测定藤黄酸在15 d内的稳定性;雄性Wistar大鼠尾静脉分别注射1 mg/m L藤黄酸、藤黄酸脂质体后,采用UPLC-MS/MS方法测定血药浓度,比较2种药物药动学参数差异。结果 Box-Behnken优化后脂质体最优处方为胆固醇444 mg、蛋黄磷脂酰胆碱1 823 mg和二硬脂酰基磷脂酰乙醇胺-聚乙二醇705 mg,脂质体包封达到92.3%,脂质体粒径均一,表面光滑;体外释放结果表明脂质体可以平缓释放,且具有长效作用,在15 d内储存稳定;脂质体中藤黄酸的体内半衰期为9.97 h,是藤黄酸的4.43倍;脂质体中藤黄酸的AUC0~24 h为22.55μg·h/m L,是藤黄酸的4.73倍。结论藤黄酸脂质体与原料药相比具有长循环、血药浓度高、释放平缓等特点。
OBJECTIVE: To optimize the preparation process of gambogic acid long-circulating liposomes and to study its in vitro release and in vivo pharmacokinetics. Methods Quantitative determination of gambogic acid was established. Using the entrapment efficiency of gambogic acid as an indicator, the prescription of liposomes was optimized by the Box-Behnken test. The best encapsulation efficiency of gambogic acid was obtained. Scanning electron microscope Acid liposome surface morphology, dialysis method of liposome in vitro release was measured to determine the stability of gambogic acid within 15 d; male Wistar rat tail vein injection of 1 mg / m L Gambogic acid, Garcinia After acid liposomes, the plasma concentration was determined by UPLC-MS / MS, and the pharmacokinetic parameters of the two drugs were compared. Results The optimum formulation of optimized liposomes of Box-Behnken was 444 mg of cholesterol, 1823 mg of egg yolk phosphatidylcholine and 705 mg of distearoylphosphatidylethanolamine-polyethylene glycol, the liposome encapsulation reached 92.3% The liposomes were uniform in size and smooth in surface. The results of in vitro release showed that the liposomes could release slowly and had long-lasting effect and were stable in storage within 15 days. The half-life of gambogic acid in liposomes was 9.97 h, 4.43 times higher than that of yellow acid. AUC0 ~ 24 h of gambogic acid in liposomes was 22.55 μg · h / m L, which was 4.73 times of that of gambogic acid. Conclusion Gambogic acid liposomes have the characteristics of long circulation, high blood concentration and smooth release compared with the original drug.