齐墩果酸纳米脂质体的制备及其大鼠体内药动学

目的: 制备齐墩果酸纳米脂质体,初步考察其在大鼠体内的药动学行为。 方法: 采用逆相蒸发法制备齐墩果酸纳米脂质体并对其进行表征,采用葡聚糖凝胶柱色谱法测定包封率。大鼠尾静脉注射齐墩果酸纳米脂质体和自制齐墩果酸溶液,以原人参二醇为内标物,采用HPLC测定不同时间血浆中齐墩果酸含量,采用PK-Solver2.0药动学软件进行非房室模型处理,并将药动学参数进行统计学分析。 结果: 制得的脂质体为圆形或类圆形的小囊泡,平均粒径(98.11±0.32) nm,包封率(81.2±1.21)%。与齐墩果酸溶液相比,齐墩果酸纳米脂质体静脉注射后,其t1/2和MRT延长,AUC_0-t提高,CL_{_obs}降低。 结论: 制备的齐墩果酸纳米脂质体具有较小粒径和较高包封率,显著提高了齐墩果酸的生物利用度,延长了其在体内的滞留时间。

Preparation of Oleanolic Acid Nanoliposomes and Its Pharmacokinetics Investigation in Rats

Objective: To prepare oleanolic acid nanoliposomes and investigate its in vivo pharmacokinetics behavior in rats. Method: Oleanolic acid nanoliposomes were prepared by reverse-phase evaporation and characterized,entrapment efficiency was determined by sephadex column chromatography.Rats were injected with oleanolic acid nanoliposomes and oleanolic acid solution prepared by ourselves via the tail,respectively.The plasma concentrations of oleanolic acid from samples were determined by HPLC,with protopanaxadiol as internal standard.Pharmacokinetic parameters and non-compartment models were analyzed by t-test and PK-Slover 2.0 software,respectively. Result: Oleanolic acid nanoliposomes were round or oval vesicles with the mean diametre of (98.11±0.32) nm and encapsulation efficiency of (81.2±1.21)%.The plasma concentration-time curves of the nanoliposomes and solution conformed to non-compartmental model.By comparing with oleanolic acid solution,t1/2 and MRT of oleanolic acid nanoliposomes extended,AUC_0-t increased and CL_{_obs} decreased. Conclusion: Oleanolic acid nanoliposomes with high entrapment efficiency and small particle size had significantly improved bioavailability of oleanolic acid and prolonged its in vivo retention time.