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目的:研究阿苯达唑自微乳(ABZ-SMEDDS)在Caco-2细胞上的吸收机制。方法:以阿苯达唑(ABZ)作对照,利用Caco-2细胞模型考察时间、药物浓度以及有或无P-gp和BCRP专属性抑制存在时其摄取特征,同时考察了处方中药用辅料:聚氧乙烯35氢化蓖麻油(EL)和乙二醇单乙基醚(HP)对Caco-2细胞摄取及新剂型双向转运特征的影响。以上均采用HPLC法对Caco-2细胞摄取和转运作定量分析,并计算其表观渗透系数(Papp)以及跨膜电阻值的变化。结果:ABZ-SMEDDS在Caco-2细胞模型上的是以被动扩散为主要吸收方式,药物摄取量与时间、浓度呈正相关,在相同药物浓度下ABZ-SMEDDS的摄取量明显高于ABZ(P<0.05)。P-gp和BCRP专属抑制剂维拉帕米(VER)、烟曲霉素C(FTC)均能够显著增加细胞对ABZ摄取量(P<0.01),但对ABZ-SMEDDS的细胞摄取量无影响(P>0.05);EL和HP均可以增加ABZ的摄取量。双向转运表观渗透系数:PappBtoA/PappAtB<1.5,且Papp(ABZ-SMEDDS)>Papp(ABZ)。结论:ABZ在Caco-2细胞上以被动扩散的方式吸收,同时存在可能由P-gp和BCRP介导的主动转运,自微乳制剂能促进ABZ的吸收。
OBJECTIVE: To study the absorption mechanism of albendazole self-microemulsion (ABZ-SMEDDS) on Caco-2 cells. Methods: Using ABZ as control, the uptake characteristics of Caco-2 cells were observed by using Caco-2 cell model with time, drug concentration and the specificity of P-gp and BCRP with or without inhibition. Meanwhile, Effects of polyoxyethylene 35 hydrogenated castor oil (EL) and ethylene glycol monoethyl ether (HP) on uptake of Caco-2 cells and bidirectional transport characteristics of new dosage forms. The uptake and translocation of Caco-2 cells were quantitatively analyzed by HPLC and the changes of Papp and transmembrane resistance were calculated. RESULTS: ABZ-SMEDDS was mainly absorbed by passive diffusion in Caco-2 cell model. The uptake of ABZ-SMEDDS was positively correlated with time and concentration. ABZ-SMEDDS uptake was significantly higher than ABZ at the same drug concentration (P < 0.05). Both P-gp and BCRP-specific inhibitors, verapamil (VER) and fumagillin C (FTC), significantly increased cell uptake of ABZ (P <0.01), but had no effect on cellular uptake of ABZ-SMEDDS (P> 0.05). Both EL and HP increased ABZ uptake. Bidirectional transport Apparent permeability coefficient: PappBtoA / PappAtB <1.5 and Papp (ABZ-SMEDDS)> Papp (ABZ). CONCLUSION: ABZ is absorbed by passive diffusion in Caco-2 cells. At the same time, ABZ can be actively transported by P-gp and BCRP. Self-microemulsion can promote the absorption of ABZ.