莪术醇柔性脂质体雾化吸入剂的制备及体内外评价

Preparation of curcumol flexible liposomes for nebulized inhalation and in vitro and in vivo evaluation

目的制备雾化吸入的莪术醇柔性脂质体,优化其处方工艺,对其进行表征并测定其对细胞增殖的影响和肺部靶向性。方法以包封率为主要考察指标,筛选脂质体的制备方法,以微柱离心-气相法测定其包封率,研究药脂比、膜材比、旋蒸温度、水化温度等因素对脂质体包封率的影响;通过正交实验对处方和工艺进行优化,并进行质量评价。以TGF-β1诱导的A549上皮细胞为模型,通过IncuCyte平台进行细胞抑制率实验。采用雾化吸入的给药方式,测定莪术醇柔性脂质体的体内分布。结果采用薄膜水化法进行莪术醇柔性脂质体的制备,优化后的制备处方为药脂比1∶30,不加胆固醇,平均包封率为83.92%,平均粒径为0.116μm。体外释放研究表明,莪术醇柔性脂质体相比游离莪术醇具有缓释效果。细胞增殖实验表明莪术醇柔性脂质体对TGF-β1诱导的A549上皮细胞的抑制作用高于游离莪术醇。雾化吸入的莪术醇柔性脂质体具有更好的肺部靶向性。结论优选处方制备的莪术醇柔性脂质体包封率高、粒径小且均匀,具有良好的肺部靶向性。

Objective To prepare curcumol flexible liposomes for nebulized inhalation,optimize their prescription process,characterize them,and determine their effect on the cell proliferation and lung targeting.Methods The encapsulation ratio was used as the main index.The liposome preparation methods were screened,and the encapsulation ratio was determined by microcolumn centrifugation-gas chromatography.The effect of drug-lipid ratio,membrane material ratio,spinning temperature,and hydration temperature on the encapsulation ratio of liposomes was determined.The prescription and process were optimized by orthogonal test,and the quality was evaluated.TGF-β1-induced A549 epithelial cells were used as models,and cytostatic rate experiments were conducted with the IncuCyte platform.The in vivo distribution of curcumol loaded in flexible liposomes was determined after administering nebulized inhalation.Results The curcumol flexible liposomes were prepared by film hydration.The optimized prescription was a 1∶30 drug-lipid ratio(without cholesterol),with an average encapsulation raito of 83.92%and an average particle size of 0.116μm.In vitro release studies showed that curcumol flexible liposomes had a slower release than that of free curcumol.Cell proliferation experiments showed that curcumol flexible liposomes inhibited TGF-β1-induced A549 cells more than did free curcumol.The curcumol flexible liposomes for nebulized inhalation better targeted at the lung.Conclusion Curcumol flexible liposomes prepared by the optimized prescription have a high encapsulation raito,small and uniform particle size,and good lung targeting effect.