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目的研究乳糖化-去甲斑蝥素(Lac-NCTD)及其壳聚糖纳米粒(Lac-NCTD-NPs)的细胞摄取、转运机制。方法采用Caco-2细胞单层模型研究Lac-NCTD和Lac-NCTD-NPs的摄取和跨膜转运,考察了时间、温度、pH值、药物质量浓度、吸收抑制剂和促进剂对药物跨膜吸收的影响,并比较两种剂型吸收过程的差异。结果 Lac-NCTD以主动转运为主要方式被细胞摄取和转运,少部分通过旁路转运。药物的摄取和时间呈正相关,与温度呈负相关。P-糖蛋白(P-gp)和多药耐药相关蛋白2(MRP2)抑制剂能增加Lac-NCTD的细胞摄取(P<0.05)。药物从基底侧(basolateral,BL)到肠腔侧(apical,AP)的渗透系数(Papp(BL→AP))大于Papp(AP→BL)。内吞抑制剂氧化苯砷对药物的转运无影响,旁路转运促进剂去氧胆酸钠能增加药物转运。结论 Lac-NCTD主要以主动转运方式被吸收,少部分通过旁路转运被Caco-2细胞摄取和转运,此过程受P-gp和MRP2外排蛋白的影响,且药物纳米粒的摄取和转运较其溶液均有增加。
Objective To study the cellular uptake and transport mechanisms of Lac-NCTD and Lac-NCTD-NPs. Methods Caco-2 cell monolayers were used to investigate the uptake and transmembrane transport of Lac-NCTD and Lac-NCTD-NPs. The effects of time, temperature, pH, drug concentration, absorption inhibitor and accelerator on the transmembrane absorption The differences between the two dosage forms were compared. Results Lac-NCTD was mainly taken up and transported by cells by active transport, and a little by bypass. Drug intake was positively correlated with time and negatively correlated with temperature. P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) inhibitors increased cellular uptake of Lac-NCTD (P <0.05). The permeability coefficient (Papp (BL → AP)) of the drug from the basolateral (BL) to the apical (AP) side is greater than Papp (AP → BL). Endocytosis inhibitor benzene and arsenic did not affect drug transport, bypass transport enhancer sodium deoxycholate can increase drug transport. Conclusions Lac-NCTD is mainly absorbed by the active transporter, and a small part of the Lac-NCTD is taken up and transported by the Caco-2 cells via the bypass transport. This process is affected by the efflux of P-gp and MRP2, and the uptake and transport of the drug nanoparticles The solution has increased.