Caco-2细胞单层模型构建及3种药物吸收机制评价

Construction of Caco-2 Cell Monolayer Model and Absorption Mechanism Evaluation of Three Kinds of Drugs

目的:研究3种不同特性药物体外Caco-2细胞转运及其机制.方法:构建Caco-2细胞单层模型,选择酚酸类药物丹参总酚酸,生物碱类药物盐酸小檗碱和皂苷类药物三七皂苷R1为模型药物,研究3种不同特性药物经Caco-2细胞单层膜转运特点,分析其转运机制.结果:丹参总酚酸在酸性条件下经Caco-2细胞单层膜转运较高,无外排机制.盐酸小檗碱外排机制较强,不受pH的影响.三七皂苷R1经Caco-2细胞转运较差,但无外排机制,不受pH的影响.结论:3种药物口服吸收均较差,但机制不同.提高3种药物口服吸收的措施:提高丹参总酚酸在胃中滞留时间;消除盐酸小檗碱的外排影响;改善三七皂苷R1的膜透性.

Objective The transport mechanism of 3 kinds of drugs across Caco-2 cells in vitro were studied. Method Caco-2 cell monolayer model was constructed.Salvianolic acids (phenolic acid drugs), berberine hydrochloride (alkaloids drugs) and notoginsenoside R1 (saponins drugs) were selected as model drugs.Transport characteristics of three kinds of drugs transport across Caco-2 cell monolayer were studied and their transport mechanism was analyzed.Result Salvianolic acids was highly transported across Caco-2 cell monolayer under acidic conditions without efflux effect.The efflux effect of berberine hydrochloride was strong, the transport was not affected by pH of the transport media.Notoginsenoside R1 was poorly transported across Caco-2 cells, but had no efflux effect and was not affected by pH of the transport media.Conclusion Oral absorption of the three drugs is not good, what’s more, the mechanism is different.The strategies to improve the three drugs oral absorption are as follows: Improving the retention time of salvianolic acids in stomach;Reducing the efflux of berberine hydrochloride;Improving lipophilicity of notoginsenoside R1.