胆汁酸替代胆固醇制备盐酸伊立替康脂质体的可行性研究

Feasibility of Replacing Cholesterol by Bile Acids to Prepare Irinotecan Hydrochloride Liposomes

目的:探讨用胆汁酸代替胆固醇制备盐酸伊立替康脂质体的可行性,并优化制备工艺处方,减少胆固醇的使用。方法:以薄膜分散法制备含不同比例的胆汁酸-胆固醇的盐酸伊立替康脂质体,采用Sephadex G-50凝胶色谱法分离游离的盐酸伊立替康和脂质体,进行高效液相分析,计算脂质体的包封率(EE)和载药量(DL)。以包封率、载药量,粒径和分散性指数(PDI)评价胆汁酸对脂质体的影响。最后以胆酸为代表,采用Box-Behnken实验设计法优化胆酸-盐酸伊立替康脂质体的工艺处方,对优化后的脂质体进行表征。结果:在不同胆汁酸-胆固醇比例下制备的盐酸伊立替康脂质体均具有类似于传统脂质体(胆固醇型)的EE、DL、粒径和PDI,经过处方优化后的胆酸-盐酸伊立替康脂质体为类球形,EE为82.04%±1.38%,DL为3.72%±0.04%,粒径为(154.16±4.92)nm,PDI为0.15±0.02,剪切面电位为(-56.93±0.46)mV,在体外表现出缓释作用。结论:胆汁酸可以作为膜材料辅料,应用于脂质体的制备,降低胆固醇的使用量。

Objective:To study the feasibility of preparing irinotecan hydrochloride liposomes with bile acids instead of cholesterol,and optimize the preparation process prescription to lower the usage of cholesterol.Methods:Irinotecan hydrochloride liposomes containing different ratios of bile acid-cholesterol were prepared by film dispersion method.Unencapsulated irinotecan hydrochloride and liposomes were separated by Sephadex G-50 gel chromatography,and then analyzed by HPLC to calculate the encapsulation efficiency(EE)and drug loading(DL).The influence of bile acids on liposomes was evaluated in terms of EE,DL,particle size and polydispersity index(PDI).Finally,the Box-Behnken experimental design method was used to optimize the preparation process of irinotecan hydrochloride liposomes with cholic acid,and the optimized liposomes were characterized.Results:Irinotecan hydrochloride liposomes prepared at different bile acid-cholesterol ratios had similar EE,DL,particle size and PDI as conventional liposomes(cholesterol type).And irinotecan hydrochloride liposomes after optimization were spherical.Its EE was 82.04%±1.38%,DL was 3.72%±0.04%,particle size was(154.16±4.92)nm,PDI was(0.146±0.018),Zeta potential was(-56.93±0.46)mV,and it exhibited sustained release in vitro.Conclusion:Bile acids can be used as excipients for membrane materials and applied in the preparation of liposomes to reduce the use of cholesterol.