冰片修饰的葛根素脂质体的制备及脑组织分布研究  

Preparation and Brain Distribution of Borneol Modified Puerarin Liposomes

作　　者：叶晓莉[1] 吴梅君[1] 王丛瑶[2] 王晓楠[1] 封菲[1] 高越[1] YE Xiaoli;WU Meijun;WANG Congyao;WANG Xiaonan;FENG Fei;GAO Yue(Hangzhou First People’s Hospital,Hangzhou 310006,China;The First People’s Hospital of Xiaoshan District,Hangzhou 311200,China)

机构地区：[1]杭州市第一人民医院,杭州310006 [2]杭州市萧山区第一人民医院,杭州311200

出　　处：《中国现代应用药学》2023年第5期632-637,共6页Chinese Journal of Modern Applied Pharmacy

基　　金：杭州市医学重点学科(OO20200055);浙江省中医药科技计划项目(2014ZA083,2021ZA111);浙江省卫生健康科技计划项目(2021KY865);杭州市卫生科技计划项目(A20210186);浙江省药学会医院药学专项科研基金项目(2020ZYY28)。

摘　　要：目的制备冰片(borneol,BO)修饰的葛根素(puerarin,Pue)脂质体(BO-Pue-Lips),进行理化性质考察及大鼠体内脑组织分布研究。方法采用薄膜分散法制备BO-Pue-Lips,通过正交设计,以包封率和载药量为评价指标优化处方工艺。以Pue混悬液和(BO-Pue)混悬液为对照组,测定大鼠尾静脉给药BO-Pue-Lips的脑组织浓度。结果制备BO-Pue-Lips的优化条件为Pue与卵磷脂质量比为1∶10,胆固醇与卵磷脂质量比为1∶4,制备温度为40℃。按优化条件所制备的BO-Pue-Lips粒径为(112.97±0.89)nm,Zeta电位为(–7.48±0.49)mV,包封率为(73.47±1.75)%,载药量为(5.55±0.13)%,药物释放曲线符合Weibull方程模型。脑组织分布结果显示,Pue、BO-Pue和BO-Pue-Lips的T1/2分别为(0.61±0.22)h,(0.55±0.27)h和(1.80±0.17)h,AUC0→t分别为(68.59±1.09)μg·h·g^(-1),(72.70±2.63)μg·h·g^(-1)和(137.68±10.17)μg·h·g^(-1),CL分别为(0.29±0.01)L·h^(–1)·kg^(-1),(0.27±0.02)L·h^(–1)·kg^(-1)和(0.13±0.01)L·h^(–1)·kg^(-1),MRT分别为(0.93±0.05)h,(0.97±0.02)h和(1.80±0.05)h。结论采用薄膜分散法成功制备了BO-Pue-Lips,确定了最优制备处方和制备工艺。BO-Pue-Lips给药后显著提高葛根素脑组织蓄积量,延长药物在脑中的滞留时间,具有良好的脑靶向性。OBJECTIVE To prepare borneol modified puerarin liposomes(BO-Pue-Lips) with optimization,and evaluate the concentration in brain of the drug liposomes in rats.METHODS The BO-Pue-Lips were prepared with the thin-film rehydration method and were optimized through orthogonal test according to entrapment efficiency and drug loading of BO-Pue-Lips.Using puerarin(Pue) suspension and borneol puerarin(BO-Pue) suspension as control,the concentration in brain of BO-Pue-Lips after intravenous administration in rats were studied.RESULTS The optimal conditions for preparation of BO-Pue-Lips were Pue-soybean phospholipids(1︰10),cholesterol-soybean phospholipids(1︰4),and the hydration temperature was 40℃.The mean particle size of the resulted BO-Pue-Lips was (112.97±0.89)nm and Zeta potential was (–7.48±0.49)mV,the average entrapment efficiency and drug-loading was (73.47±1.75)%and (5.55±0.13)%,respectively.The profiles of release in vitro was expressed well by Weibull equation.Results of distribution in brain showed that T1/2of Pue,BO-Pue and BO-Pue-Lips were (0.61±0.22)h,(0.55±0.27)h and (1.80±0.17)h,AUC0→twere (68.59±1.09)μg·h·g^(-1),(72.70±2.63)μg·h·g^(-1)and(137.68±10.17)μg·h·g^(-1),CL were (0.29±0.01)L·h^(–1)·kg^(-1),(0.27±0.02)L·h^(–1)·kg^(-1)and (0.13±0.01)L·h^(–1)·kg^(-1),MRT were (0.93±0.05)h,(0.97±0.02)h and (1.80±0.05)h.CONCLUSION An optimized liposomes drug delivery system is obtained by thin-film rehydration method.The preparation and preparation process are selected and optimized.The liposomes after intravenous administration might increase the concentration,prolong circulation time and have a good targeting efficiency in brain.

关 键 词：冰片 葛根素 脂质体 正交设计 脑组织分布 

分 类 号：R944[医药卫生—药剂学]