甘草次酸衍生物配体18-GA-Ala介导脂质体的制备及肝靶向性研究  

Preparation and Liver Targeting study of Liposomes Mediated by Glycyrrhetinic Acid Derivative Ligand 18-GA-Ala

作　　者：金粟 顾蘅[2] 董人华 王秀丽[1] 李耿 曲舒显 JIN Su;GU Heng;DONG Ren-hua;WANG Xiu-li;LI Geng;QU Shu-xian(Beijing University of Chinese Medicine,Beijing 100102,China;Department of Traditional Chinese Medicine Pharmacy,Kunming Municipal Hospital of Traditional Chinese Medicine,Kunming 650011,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)

机构地区：[1]北京中医药大学,北京100102 [2]昆明市中医医院中药房,云南昆明650011 [3]中国医学科学院,北京协和医学院,药用植物研究所,北京100193

出　　处：《中国现代中药》2023年第4期867-873,共7页Modern Chinese Medicine

基　　金：国家自然科学基金项目(81202928)。

摘　　要：目的:合成制备甘草次酸衍生物配体丙氨酸丁二酸甘草次酸十八烷酯(18-GA-Ala),并修饰包埋药物丹酚酸B(Sal B)和丹参酮ⅡA(TSN)的脂质体,探讨该脂质体对小鼠的肝靶向作用。方法:采用薄膜分散-高压乳匀法制备18-GA-Ala配体修饰的TSN-Sal B脂质体及未修饰配体的脂质体,考察粒径、电位、包封率、多分散系数和配体结合率;尾静脉给药后不同时间点获取血浆样本及小鼠心、肝、脾、肺、肾组织样本,超高效液相色谱法测定各样本中Sal B和TSN的含量,评价18-GA-Ala配体的肝靶向效果。结果:配体18-GA-Ala修饰后的脂质体中,Sal B在肝脏的药时曲线下面积(AUC)分别是脾、肺和肾的1.19、1.39、63.67倍,TSN在肝脏的AUC分别为脾、肺、肾的4.64、0.36、14.12倍。结论:甘草次酸衍生物配体18-GA-Ala修饰后的脂质体可增加Sal B和TSN在肝脏中的峰浓度,表现出一定的肝靶向作用。Objective:This study aimed to synthesize and prepare glycyrrhetinic acid derivative ligand alaninebutanedioic acid-glycyrrhetinic acid octadecenoate(18-GA-Ala)for modifying the liposomes embedded with salvianolic acid B(Sal B)and tanshinoneⅡA(TSN)and to further explore the liver targeting effect of the liposomes in mice.Methods:18-GA-Ala ligand modified TSN-Sal B liposomes and unmodified liposomes were prepared by thin film dispersion-high pressure homogenization method.The particle size,zeta potential,entrapment efficiency,polydispersity coefficient and ligand binding rate were investigated.Plasma samples and heart,liver,spleen,lung and kidney tissue samples were collected from mice at different time points after intravenous administration,and the contents of Sal B and TSN in each sample were determined by UPLC to evaluate the liver targeting effect of 18-GA-Ala ligand.Results:After administration with 18-GAAla modified liposomes,the area under the cure(AUC)of Sal B in the liver was 1.19,1.39,63.67 times that of the spleen,lung and kidney,respectively.;the AUC of TSN in the liver was 4.64,0.36,14.12 times that of the spleen,lung and kidney,respectively.Conclusion:Glycyrrhetinic acid derivative ligand 18-GA-Ala modified liposomes can increase the peak concentrations of Sal B and TSN in the liver,showing a certain liver targeting effect.

关 键 词：甘草次酸衍生物 脂质体 主动肝靶向 靶向效率 年版 丹参酮Ⅱ_(A) 

分 类 号：R282[医药卫生—中药学]