黄芩苷-小檗碱复合物及纳米晶在Caco-2细胞单层模型的吸收特性研究

Absorption properties of baicalin-berberine complex and nanocrystals in Caco-2 monolayer model

[目的]研究黄芩苷(BA)-小檗碱(BBR)复合物及纳米晶的吸收特性,探讨纳米晶技术对BA-BBR复合物吸收特性的改善。[方法]利用Cell Counting Kit-8(CCK-8)法筛选BA-BBR复合物及纳米晶对人结肠腺癌细胞系(Caco-2)细胞的给药浓度,构建Caco-2细胞单层模型探究BA-BBR复合物及纳米晶的跨膜转运方式,并且加入P-糖蛋白(P-gp)抑制剂维拉帕米研究对其累积转运量和表观渗透系数(Papp)的影响。[结果]复合物组中BA和BBR的Papp值均低于物理混合物组;与复合物组相比,纳米晶组中BA和BBR的累积转运量和Papp值均提高,Papp值为复合物组的1.3倍和2.3倍。加入维拉帕米后,复合物组BA和BBR的Papp值分别提高1.5倍和2.0倍,而纳米晶组Papp值无明显提高。[结论]BA-BBR复合物不同于物理混合物,具有低渗透性,同时易受到P-gp外排影响。纳米晶技术可以显著改善BA-BBR复合物的渗透性,并且减弱外排作用对其的影响。

[Objective]The absorption properties of Baicalin(BA)-Berberine(BBR)complex and nanocrystals were studied,and the improvement of nanocrystals technology on the absorption properties of BA-BBR complex was discussed.[Methods]The concentration of the BA-BBR complex and nanocrystals on Caco-2 cell-line were selected by CCK-8 method.The Caco-2 cell monolayer model was constructed to explore the membrane transport of BA-BBR complex and nanocrystals.The influence of P-gp inhibitor verapamil on the cumulative transport volume and apparent permeability coefficient(Papp)was further studied.[Results]Pappvalues of BA and BBR in the complex group were lower than those in the physical mixture group.Compared with the complex group,the cumulative amount transported and Pappvalues of BA and BBR in nanocrystals group were significantly increased.Pappvalues of BA and BBR in nanocrystals were 1.3 and 2.3 times than those in the complex group,respectively.After verapamil addition,Pappvalues of BA and BBR were increased by 1.5 and 2.0 times separately in BA-BBR complex,while not significantly increased in nanocrystals.[Conclusion]Unlike physical mixtures,BA-BBR complex exhibited low permeability and high susceptibility on P-gp efflux.Nanocrystals could achieve the significantly permeability improvement and efflux reduction of BA-BBR complex.