半乳糖化胆固醇配体修饰去甲斑蝥素脂质体的制备及表征  

Preparation and Characterization of Galactosylated Cholesterol Ligand Modified Liposomes Containing Norcantharidin

作　　者：周卿 史大斌 梅世露 杨鑫 ZHOU Qing;SHI Dabin;MEI Shilu;YANG Xin(Teaching and Research Section of Pharmaceutical Analysis,Pharmacy School,Zunyi Medical University,Zunyi 563003;Teaching and Research Section of Pharmaceutical Chemistry,Pharmacy School,Zunyi Medical University,Zunyi 563003)

机构地区：[1]遵义医科大学药学院药物分析教研室,贵州遵义563003 [2]遵义医科大学药学院药物化学教研室,贵州遵义563003

出　　处：《中国医药工业杂志》2019年第10期1208-1214,共7页Chinese Journal of Pharmaceuticals

基　　金：贵州省自然科学基金(黔科合J字[2018]2150号)

摘　　要：以半乳糖和胆固醇氯甲酸酯为底物,通过化学反应合成半乳糖-胆固醇偶联物,并经1H NMR、13C NMR和HRMS确证了产物的结构。以此为配体,采用薄膜超声分散法制备半乳糖化胆固醇配体修饰的去甲斑蝥素脂质体,通过单因素试验和正交设计优化处方。结果所得优化工艺为:磷脂与半乳糖化胆固醇的质量比3∶1,药脂比1∶12,溶胀时间30 min。优化脂质体的包封率为(50.75±1.61)%,载药量为(7.85±2.16)%,平均粒径为(128.4±5.7)nm,平均ζ电位(-22.78±1.80)mV;与去甲斑蝥素溶液相比,优化脂质体的体外释放呈现出一定的缓释特征。In order to improve the bioavailability and initiate target efficiency of norcantharidin, a new conjugate of galactose and cholesterol was synthesized and adopted to prepare the liposomes loaded with norcantharidin. The structure of the conjugate was confirmed by 1 H NMR, 13 C NMR and HRMS. We expected that the asialoglycoprotein receptor on the surface of hepatic parenchymal cell membrane could specifically recognize the carrier containing galactose at the terminal group, so that norcantharidin could be actively targeted to liver tissue, thereby increasing the drug concentration in liver tissue. The galactosylated cholesterol modified norcantharidin liposomes(Gal-NCTD-Lips) were prepared by thin-film ultrasonic dispersion method, and its formulation was optimized by single factor test and orthogonal design. The optimum formulation was as following: weight ratio of phospholipid to galactosylated cholesterol was 3∶1, weight ratio of lipid to drug was 12∶1, the swelling time was 30 min. The encapsulation efficiency of the optimal GalNCTD-Lips was(50.75±1.61)% with drug loading of(7.85±2.16)%, and the average diameter was(128.4±5.7)nm with ζ potential of(-22.78±1.80)mV. In vitro release results showed that the liposomes had good sustained-release characteristics compared with norcantharidin solution.

关 键 词：半乳糖化胆固醇 脂质体 去甲斑蝥素 薄膜超声分散法 

分 类 号：R944.9[医药卫生—药剂学]