薄膜-超声法制备黄芩苷脂质体及其大鼠体内药动学研究

Preparation of Baicalin Liposomes by Thin Film Ultrasonic Method and its Pharmacokinetics in Rats

目的:制备黄芩苷脂质体,进行体外质量评价及其在大鼠体内的药动学研究。方法:采用薄膜分散法制备黄芩苷脂质体,以包封率作为评价指标,通过BBD设计-效应面法,得到最佳制备的工艺参数和处方,并测定脂质体的粒径分布、包封率以及在体外药物释放情况;通过大鼠尾静脉注射黄芩苷溶液及黄芩苷脂质体溶液,分析大鼠体内的药动学参数变化情况。结果:黄芩苷脂质体的最佳工艺处方:大豆卵磷脂药物质量比例4.9∶1,大豆卵磷脂胆固醇质量比例7.53∶1,水化体积为8.07 m L;黄芩苷脂质体平均粒径在176 nm,平均包封率为41.31%,黄芩苷脂质体具有一定的缓释作用;黄芩脂质体组在大鼠体内的半衰期(t_(1/2))延长,药时曲线下面积AUC(0~t)、AUC(0~∞)增加以及体内平均滞留时间延长,说明将黄芩苷制备成脂质体后作用可提高药物的疗效。结论:制备的黄芩苷脂质体具备一定的缓释性能,对黄芩苷新剂型的开发及临床研究具有重要意义。

Objective:Baicalin liposomes were prepared,the quality was evaluated in vitro,and the changes of pharmacokinetic parameters in rats were observed.Methods:Baicalin liposomes were prepared by thin-film dispersion method.Taking the entrapment efficiency as the evaluation index,through single factor correlation investigation and star point design response surface method,taking the drug phospholipid ratio,hydration volume and lipid ratio as the three factors of the response surface,the optimal preparation process parameters and formulation were obtained,and the particle size distribution and Entrapment efficiency and drug release in vitro;The changes of pharmacokinetic parameters of baicalin solution and baicalin liposome solution in rats were analyzed and compared.Results:The optimum formulation of baicalin liposome:the ratio of soybean lecithin to drug is 4.9∶1,the ratio of soybean lecithin to cholesterol is 7.53∶1,and the hydration volume is 8.07 m L;The average particle size of baicalin liposome was 176 nm and the average entrapment efficiency was 41.31%;The half-life(t_(1/2))of baicalin liposome group in rats was prolonged,the area under the drug time curve AUC(0~t),AUC(0~∞)and the average residence time in vivo were increased,indicating that baicalin can improve the curative effect of the drug after preparation into liposome.Conclusion:The prepared baicalin liposomes have certain sustained-release properties,which is of great significance for the development and clinical research of new dosage forms of baicalin.