甘草次酸衍生物18GAGly介导肝主动靶向脂质体的制备及体内相关研究.docVIP

甘草次酸衍生物18GAGly介导肝主动靶向脂质体的制备及体内相关研究 　　[摘要]基于国内外对甘草次酸配体介导主动肝靶向脂质体的研究情况，该文主要对以甘草次酸为母核的肝靶向配体18GAGly修饰的脂质体的肝靶向效果进行研究。采用薄膜分散高压乳匀法制备18GAGly配体介导的丹参酚酸B丹参酮ⅡA脂质体及未修饰配体的脂质体，考察2种脂质体的制剂学性质，考察粒径、电位、包封率和配体结合率；尾静脉给药后不同时间点获取血浆样本以及小鼠心、肝、脾、肺、肾组织样本，UPLC测定各样本中丹参酚酸B（Sal B）和丹参酮IIA（TSN）含量，评价18GAGly配体的肝靶向效果。结果显示脂质体GlyTSLip和TSLip的粒径、电位、包封率、配体结合率基本符合要求；体内靶向性考察结果显示GlyTSLip组脂质体与TSLip组脂质体血浆数据无显著性差别；甘草次酸衍生物配体18GAGly介导脂质体可以增加Sal B和TSN 在肝组织的峰浓度，但并未显示明显的肝靶向效果。 　　[关键词]甘草次酸衍生物； 脂质体； 主动肝靶向； 靶向系数； 丹酚酸B； 丹参酮ⅡA 　　[Abstract]Based on the research of active liver targeting liposomes mediated by glycyrrhetinic acid ligand at home and abroad， this paper focuses on the liver targeting effect of liposomes mediated with 18GAGly， a kind of glycyrrhetinic acid ligand salvianolic acid B（Sal B）tanshinone ⅡA （TSN）liposomes mediated by 18GAGly as well as the liposomes with unmodified ligands were prepared by film dispersionhigh pressure homogenization method， and then the particle size， potential， encapsulation efficiency and ligand binding rate were detected Plasma samples of the heart， liver， spleen， lung and kidney tissues were taken at different time points after tail vein injections The contents of Sal B and TSN in each sample were determined with UPLC methods and the liver targeting effect of 18GAGly ligands was evaluated The results showed that the particle size， potential， encapsulation efficiency and ligand binding rate met the basic requirements； in vivo targeting investigation results showed no difference between GLYTSLip group and TSLip group The liposomes mediated by glycyrrhetinic acid derivative ligand 18GAGly can increase the peak concentration of Sal B and TSN in liver， but showed no significant liver targeting effect. 　　[Key words]glycyrrhetinic acid derivatives； liposomes； active liver targeting； targeting coefficient； salvianolic acid B； tanshinone ⅡA 　　脂?|体是一种以磷脂为膜材的具有良好生物相容性的脂质载体，属于纳米制剂的一种，在静脉注射入体内后会因被动靶向作用向网状内皮系统丰富的组织分布[1]。通过在脂质体表面进行一定修饰，可以实现特定组织部位的聚集。研究表明甘草次酸衍生物是良好的肝靶向配体，特别是对甘草次酸3位和30位进行一定的