齐墩果酸膜修饰脂质体的制备及其在大鼠体内药动学  

Preparation of membrane-modified liposomes loaded with oleanolic acid and its pharmacokinetics in rats

作　　者：倪斌[1] 李翔[1,2] 张婧[1] 廖正根[1] 罗云[1] 赵海平[1] 

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]江西中医药大学中药固体制剂制造技术国家工程研究中心,江西南昌330006

出　　处：《中国医院药学杂志》2014年第18期1566-1571,共6页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:81202927);江西省青年科学基金资助项目(编号:20114BAB215038;20132BAB215022);江西省教育厅青年基金项目(编号:GJJ12536;GJJ12535)

摘　　要：目的:制备齐墩果酸膜修饰脂质体,并对其体内药动学行为进行研究。方法:以合成的高荷电密度的N-三甲基壳聚糖(TMC)为脂质体膜修饰材料,通过FT-IR、1 H-NMR对合成产物进行结构确证;采用乙醇注入法制备TMC修饰的齐墩果酸脂质体(OA-TCL),采用微柱离心、透射电镜、粒径Zeta电位测定仪考察OA-TCL的理化性质,并对OA-TCL口服给药后在大鼠体内药动学行为进行研究。结果:脂质体呈球形或类球形,平均粒径(164±4.24)nm,Zeta电位为(23.8±0.2)mV,包封率可达(96.8±1.76)%;药动学参数显示OA-TCL药-时曲线下面积分别为齐墩果酸混悬液组、齐墩果酸未修饰脂质体组的2.51,2.33倍。结论:该研究为进一步研究OA-TCL在急慢性肝损伤治疗中的应用提供了基础,为难溶性中药成分口服给药系统的设计提供了新思路。OBJECTIVE To prepare membrane-modified liposomes loaded with oleanolic acid and investigate the in vivo pharmacokinetics profile.METHODS A novel polymer with high density of charges,N-trimethyl chitosan（TMC）was synthesized as liposomal modifying material.The structure of the TMC was confirmed with FT-IR and ^1H-NMR.Oleanolic acid-loaded TMC-modified liposomes（OA-TCL）were prepared by ethanol injection method.The mini column centrifugation technique,transmission electron microscope,dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of OA-TCL.The concentration of OA in plasma of rats and their pharmacokinetic behaviors after oral administration were studied by RP-HPLC.RESULTS The optimized formulation was as follows：lecithin1%（g/g）,lecithin：cholesterol 4∶1（g/g）,lecithin：drug 10∶1（g/g）,temperature 50℃.OA-TCL showed spherical or ellipsoid shape.The mean particle sizes were（164±4.24）nm,Zeta potential was（23.8±0.2）mV and the drug encapsulation efficiency achieved（96.8±1.76）%.The AUC of OA-TCL was 2.51 and 2.33 fold greater than that of OA suspension and OA liposomes without membrane modification,respectively.CONCLUSION The work is useful for further research on the application of OA-TCL for acute or chronic liver injury therapy.Furthermore,it offers new ideas for the oral drug delivery system of TCM components with low solubility.

关 键 词：齐墩果酸 N-三甲基壳聚糖 膜修饰脂质体 药-时曲线 

分 类 号：R943[医药卫生—药剂学]