肝靶向索拉非尼脂质体的制备及体外抗肿瘤作用  

Preparation and in vitro Antitumor Activity of Liver-targeting Liposomes Loaded with Sorafenib

作　　者：张金坤[1] 杨阳[1] 徐蓓[2] 贺英菊[1] 宋相容[2] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]四川大学华西医院生物治疗国家重点实验室,四川成都610041

出　　处：《中国医药工业杂志》2014年第5期454-459,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然基金青年项目(81302729)

摘　　要：以甘草次酸修饰的胆固醇(GA-PEG-Chol)为肝靶向材料,采用薄膜分散法制备载索拉非尼(1)的肝靶向脂质体,并评价其制剂学相关性质、体外抗肿瘤活性及体外摄取效率。所得制品粒径和包封率为(89.79±6.20)nm和(86.13±2.75)%;在含有0.6%Tween-80的磷酸盐缓冲液(pH 7.4)中,48 h累积释放率为80%。体外抗肿瘤活性研究显示,当1浓度为10μg/ml时,肝靶向1脂质体对人肝癌细胞SMMC-7721和Bel-7402的体外生长抑制作用明显优于游离1和非靶向1脂质体(P<0.05)。体外摄取研究结果显示,上述两株肝癌细胞对肝靶向脂质体的摄取效率显著高于游离香豆素(P<0.05),提示肝靶向1脂质体增强的抗肝癌活性可能源于其显著增加了肝癌细胞内的药物浓度。The liver-targeting liposomes loaded with sorafenib （1） were prepared by thin-film dispersion method with glycyrrhetinic acid modified cholesterol （GA-PEG-Chol） as targeting agent. The related pharmaceutical properties, in vitro antitumor activity and in vitro uptake efficiency were investigated. The results showed that the mean size and the entrapment efficiency of the product were （89.79±6.20）nm and （86.13±2.75） %. The cumulative release of 1 from the product at 48 h was 80% in pH 7.4 phosphate buffer containing 0.6% Tween-80. The in vitro antitumor activity study showed that the product inhibited the growth of two human hepatoma cell lines （SMMC-7721 and Bel-7402） more effectively than the free drug and non-targeting 1 liposomes （P〈0.05） when the drug concentration was 10 ktg/ml. In the in vitro uptake assay, the liver-targeting liposomes loaded with coumarin presented the fluorescence intensity far higher than the free coumarin in both SMMC-7721 and Bel-7402 cells （P〈0.05）. These findings indicated that the enhanced antitumor activity of 1 liver-targeting liposomes probably attributed to the increasing intracellular concentration of 1.

关 键 词：索拉非尼 甘草次酸 肝靶向 脂质体 细胞毒性 细胞摄取 

分 类 号：R944.9[医药卫生—药剂学]