盐酸小檗碱纳米脂质体的优化制备方法及其体外细胞毒性研究  

The optimized preparative method of berberine hydrochloride nanoliposome and its in vivo cytotoxicity

作　　者：李彩虹[1,2] 王俊玲 周克元[1] 

机构地区：[1]广东医学院生物化学与分子生物学教研室 [2]广东省医学分子诊断重点实验室 [3]纳米技术及应用国家工程中心,广东东莞523808

出　　处：《中国药理学通报》2012年第9期1314-1318,共5页Chinese Pharmacological Bulletin

基　　金：广东省中医药局科研项目(No ZY1008);湛江市科技攻关计划项目(No 2009C3106013);东莞市科技计划项目(No200910815261);广东医学院青年基金项目(No XQ0816)

摘　　要：目的优化盐酸小檗碱脂质体制备条件,以更好解决盐酸小檗碱药物毒性和生物利用度问题。方法优化主动载药法制备盐酸小檗碱纳米脂质体,并对该脂质体进行包封率、粒径、形貌等考察,利用MTT法评价脂质体的生物安全性。结果盐酸小檗碱脂质体优化制备工艺为卵磷脂与胆固醇质量比为3∶1,药物浓度为0.8 g.L-1,孵化温度为60℃。较低浓度(≤20 mg.L-1)的该脂质体,作用于HeLa细胞48 h后,存活率在80%以上。结论利用优化工艺制备的脂质体包封率达到83%,粒径在90 nm左右,明显提高了生物利用度。48 h内该脂质体比小糪碱纯品对HeLa细胞的毒性作用小,预示这种改进的方法可能有助于改善药物的安全性。Aim To optimize the preparation conditions of berberine hydrochloride liposome, in order to improve its bioavailability and to alleviate its toxicity. Methods The BH nanoliposome were prepared by optimized active loading method. Furthermore,the entrapment efficiency, partical size and shape of those liposome were investigated. The biological safety of the liposome was evaluated by MTF assay. Results The optimized preparative protocol of BH nanoliposome was that the ratio of the quantity of Lecithin and Cholesterol was 3 to 1, the BH content of those nanoliposome was 0. 8 g · L^-1, and the hatch temperature was 60℃. The cell survival rate was maintained at more than 80%48 hours after treated by low concentration （ ≤20 mg· L^-1 ） BH nanoliposome sample. Conclusions The entrapment efficiency of the liposome prepared by the optimized process is 83% and the partical size （90 nm or thereabouts） becomes smaller than that of the reported which can improve the bioavailability of drugs. The toxic effects of the BH nanoliposome on Hela ceils is less than that of the pure berberine within 48 hours, which indicates that this improved preparative method of the nanoliposome may help to improve the safety of the drug.

关 键 词：主动载药法 盐酸小檗碱 纳米脂质体 生物安全性 生物利用度 细胞毒 

分 类 号：R282.71[医药卫生—中药学] R284.1[医药卫生—中医学]