乳糖脂修饰苦参碱脂质体的肝靶向性和体外抑瘤作用研究  

Study on targetability of lactosaminated matrine liposomes to liver in vivo and inhibition to HepG2 cells in vitro

作　　者：张方宇[1] 何松[1] 

机构地区：[1]重庆医科大学附属第二医院消化内科,重庆400010

出　　处：《重庆医科大学学报》2009年第6期747-751,共5页Journal of Chongqing Medical University

基　　金：重庆市卫生局科技基金项目(06-2-076和2006-B-31)

摘　　要：目的:制备乳糖酰磷脂酰乙醇胺修饰的苦参碱脂质体(Lactosaminated matrine liposomes,LML),考察其在小鼠体内的肝靶向性,并研究其对人肝癌细胞系HepG2细胞的体外抑制作用。方法:采用逆向蒸发-短时超声法制备苦参碱脂质体Matrine liposomes,ML),合成乳糖酰磷脂酰乙醇胺并用其修饰苦参碱脂质体得到乳糖脂苦参碱脂质体。考察其包封率及粒径,应用反相高效液相色谱法测定小鼠体内各组织中的苦参碱含量,通过MTT法检测LML对人肝癌细胞系HepG2的体外抑制作用。结果:LML形态均匀,粒径分布范围为80～150nm,包封率为48.1%。与苦参碱溶液(Matrine solution,M-sol)相比,普通苦参碱脂质体及乳糖脂苦参碱脂质体的体内循环时间明显延长,且乳糖脂苦参碱脂质体的肝脏药—时曲线下面积(Area under curve,AUC)值相对于苦参碱脂质体和苦参碱溶液具有显著性差异(P<0.05)。LML组中的肝脏相对于其它脏器的靶向效率(Targetingeffi-ciency,Te)值均大于1,是脾脏的2.7倍,是肺脏的3倍,是肾脏的6.6倍,是心脏的8.5倍,具有显著性差异(P<0.01)。MTT法分析发现,当浓度为0.5mg/ml时,LML、ML及M-sol对人肝癌HepG2细胞的杀伤率分别为51.97%、31.89%和28.34%,前一组与后两组之间有显著差异(P<0.05)。结论:本研究制备的乳糖脂苦参碱脂质体具有较好的体内肝靶向性和体外抑瘤作用,有望成为一种新型靶向抗肝癌药物。Objective：To prepare lactosaminated matrine liposomes and to study its targetability to liver in mice and efficacy of anti-tumor activities on human hepatoma cell line HepG2 in vitro. Methods： The matrine liposomes were prepared using the reverse-phase evaporation-ultrasonic technique. Lactosylphosphatidy-lethanolamine（ Lac-PE） was synthesized and used for modified matrine liposomes..the diameter and entrapment efficiency of it were determined. The RP-HPLC was used for the determination of matrine concentration in mice tissue. The cytotoxic effect of LML on human hepatoma cell line HepG2 in vitro was detected by thiazolyl blue （MTT）assay. Results ：The LML were nice and uniform,the particle diameter was between 80 and 150 nm and envelopment rats was 48.1%. Compared with matrine solution, ML and LML exhibited long circulation time. Tissue distribution results proved that the area under curve of liver was significantly difference among modified matrine liposomes, regular matrine liposomes and matrine solutions （P〈 0.05）. The accumulation of LML in the mice liver was 2.7 times as in the spleen, 3 times as in the lung, 6.6times as in the kidney, and 8.5 times as in the heart（P〈0.01）. The inhibitory rate of LML,ML and M-sol on HepG2 ceells were 51.97%, 31.89% and 28.34% at the concentrations of 0.5mg/ml, respectively. And there were markd difference between the former and the latter two（P〈0.05）. Conclusion： The preparation method of LML is simple and repeatable. LML showed a good liver-targeted efficiency in mice and high killing effects on hepatic carcinoma ceils in vitro.

关 键 词：乳糖酰磷脂酰乙醇胺 苦参碱 脂质体 肝靶向性 肝癌细胞系HEPG2 

分 类 号：R735.7[医药卫生—肿瘤]