黄芩苷前体脂质体的制备及其在大鼠体内的药动学研究

摘要

目的：优化处方及制备含脱氧胆酸钠的黄芩苷前体脂质体，并进行其在大鼠体内的药动学研究。方法：采用喷雾干燥法制备黄芩苷前体脂质体。基于Box-behnken设计的响应面法，以氢化大豆卵磷脂（HSPC）、胆固醇和脱氧胆酸钠的处方量为考察因素，以黄芩苷的包封率为考察指标，对黄芩苷前体脂质体的处方进行优化。对最优处方所制黄芩苷前体脂质体的粒径、形态学、渗漏率、稳定性及其ig 15 mg/kg后在大鼠体内的药动学（与原料药比较）进行评价。结果：最优处方中黄芩苷、HSPC、胆固醇和脱氧胆酸钠的处方量分别为100、214、68、53 mg；所制脂质体包封率的预测值和实测值分别为86.42％和84.32％，平均粒径为358.4 nm；复溶后的脂质体渗漏率低，制剂稳定性良好；与黄芩苷原料药比较，其前体脂质体的t1/2、tmax、MRT、cmax和AUC0-t均显著增加（P＜0.05或P＜0.01或P＜0.001）。结论：采用喷雾干燥法成功制备黄芩苷前体脂质体，且该制备工艺简单、优化处方可行，并可提高黄芩苷在大鼠体内的口服生物利用度。%OBJECTIVE:To prepare Baicalin proliposomes (PBA) containing sodium deoxycholate (SD) with optimized for-mulation,and to study pharmacokinetics of it in rats in vivo. METHODS:PBA were prepared by spray drying method. Response surface method based on Box-behnken design was adopted to optimize the formulation of PBA with the amount of HSPC,cholester-ol and SD as factors using entrapment efficiency of PBA as index. The particle size,morphology,leakage rate and stability of the optimal PBA were evaluated along with the pharmacokinetics of it(compared to raw materials)in rats after ig administration of 15 mg/kg. RESULTS:The optimal formulation of PBA was that the amounts of baicalin,HSPC,cholesterol and SD were 100,214, 68 and 53 mg,respectively;the predicted and practical values of entrapment efficiency were 86.42% and 84.32%,respectively, and particle size of the optimal PBA was 358.4 nm. The leakage rate of reconstituted liposomes was low and the stability of PBA was good. Compared with baicalin raw material,t1/2,tmax,MRT,cmax and AUC0-t of PBA were all increased significantly(P<0.05 or P<0.01 or P<0.001). CONCLUSIONS:PBA were prepared successfully using the spray drying method. This method is simple and easy,and the optimized formulation is feasible and can improve the oral bioavailability of baicalin.