那西肽脂质体的制备及其体外抗乙肝病毒的研究  

Preparation of nosiheptide liposomes and its inhibitory effect on hepatitics B virus in vitro

作　　者：蔡钦生[1] 黄海[1] 冯美卿[1] 周珮[1] 

机构地区：[1]复旦大学药学院,上海200032

出　　处：《药学学报》2005年第5期462-465,共4页Acta Pharmaceutica Sinica

基　　金：上海市科委重点资助项目(024319204)

摘　　要：目的　制备那西肽脂质体并了解其体外抗乙肝病毒作用。方法　以超声法和脱氧胆酸钠法制备那西肽脂质体,同时考察其包封率和粒径大小的影响因素。以HPLC测定那西肽含量,以透射电镜观察其形态,以激光散射法测定其粒径大小,以HepG2 2. 2. 15细胞模型检测那西肽脂质体对乙肝病毒HBsAg和HBeAg的抑制率。结果　采用氯仿甲醇混合液(2∶1,v/v)作溶剂的那西肽脂质体包封率高于二氧六环作溶剂的。随着那西肽与卵磷脂的重量比增大,脂质体包封率呈下降趋势。脱氧胆酸钠法中的脱氧胆酸钠可以调节脂质体粒径的大小,它与卵磷脂的重量比越大脂质体的粒径越小。添加保护剂的脂质体在-20℃放置2年后基本稳定。脂质体中那西肽质量浓度为1 25, 2 5和5 0μg·mL-1时,对HBsAg和HBeAg的抑制率分别达到(46 .9±2. 6)%, (55. 4±1 .2)%, (65±3)%和(15. 1±2 .3)%, (36 .2±1.7)%, (36 .8±2. 5)%。结论　超声法或脱氧胆酸钠法可以制备那西肽脂质体;那西肽脂质体对乙肝病毒HBsAg和HBeAg抑制效果优于游离那西肽。Aim To prepare liposomes of nosiheptide and study its ability to inhibit hepatitis B virus HBsAg and HBeAg secreted. Methods Liposomes of nosiheptide was prepared by sodium deoxycholate dialysis and sonication. Nosheptide was determined by HPLC and partical size was determined by using laser light scattering instrument. Transmission electron microscopy (TEM) was used to examine the morphology of liposomes. Its actions to inhibit hepatitis B virus HBsAg and HBeAg secreted was studied by a HBV-transfectted cell line (HepG (2) 2.2.15). Results Encapsulation efficiency of liposomes by chloroform∶methanol ((2∶1), v/v) was higher than that by dioxane. With the increase of the ratio of nosiheptide∶PC (W/W), the encapsulation efficiency of liposomes decreased with the increase of ratio of sodium deoxycholate∶PC, the liposomes partical size decreased. The liposomes kept stable at (-20 ℃) after 2 years. The drug concentrations of liposomes that inhibit HBsAg secreted by (46.9±2.6)%, (55.4±1.2)%, (65±3)% and HBeAg secreted by (15.1±2.3)%, (36.2±1.7)%, (36.8±2.5)% were 1.25, 2.5, 5.0 (μg·mL^(-1)), respectively. Conclusion Liposomes of nosheptide can be prepared by sodium deoxycholate dialysis and sonication, which ability to inhibit hepatitis B virus HBsAg and HBeAg secreted is better than nosheptide.

关 键 词：那西肽 脂质体 包封率 抗乙肝病毒 粒径大小 

分 类 号：R943.4[医药卫生—药剂学]