齐墩果酸长循环脂质体大鼠体内药动学及组织分布研究

Pharmacokinetics and Tissue Distribution of Oleanolic Acid Long Circulation Liposomes in Rats

目的研究齐墩果酸(OA)长循环脂质体在大鼠体内的药动学及组织分布。方法用薄膜超声分散法制备分别以PEG2000、PEG4000、PEG6000修饰的OA长循环脂质体,HPLC法测定血浆及组织中OA的浓度,药动学分析软件DAS2.0计算药动学参数。结果 3种OA长循环脂质体的AUC分别为4 797.03,4 536.53,4 819.69μg·min·mL^(-1),其平均值约为OA溶液及普通脂质体组的3倍和1.5倍。 t_(1/2)分别为148.35,135.15,162.98 min,其平均值约为OA溶液及普通脂质体组的2.5倍和1.5倍。长循环脂质体给药后,各组织中C_(max)的顺序为:肝>心>血>肺>脾>肾。而采用不同种类PEG制成的长循环脂质体的药动学及组织特征分布无明显差异。结论与OA溶液及普通脂质体相比,长循环脂质体可显著提高OA大鼠体内循环时间和生物利用度。

Objective To investigate pharmacokinetics behavior of oleanolic acid （OA） long circulation liposomes in rats. Methods The oleanolic acid long circulation liposomes were prepared by film dispersion method. The concentration of oleanolic acid in rats＇ plasma was determined by HPLC and the pharmacokinetics parameters were calculated using DAS 2.0 program. Results The pharmacokinetic parameters of the three tested OA long circulation liposome were 4797.03, 4536.53 and 4819.69 p^g-min＇mL-1 for AUC, which were about 3 times and 1.5 times of conventional liposomes and OA solution, respectively. The obtained tin of three OA long circulation liposomes were 148.35, 135.15 and 162.98 min, about 2.5 times and 1.5 times of conventional liposomes and OA solution, respectively. The tissue distribution of drug was in an order as follows： liver 〉 heart 〉 blood 〉 lung 〉 spleen 〉 kidney. Conclusion Compared with conventional liposomes and OA solution, the OA long circulation liposomes can significantly prolong the circulation time of OA and improve the bioavailability.