Transport mechanism of lactosyl-norcantharitin and lactosyl-norcantharitin nanoparticles across Caco-2 monolayer model / 中草药

ABSTRACT

Objective: To study the mechanisms of absorption and transport of lactosyl-norcantharitin (Lac-NCTD) and lactosyl-norcantharitin nanoparticles (Lac-NCTD-NPs) in intestinal membranes. Methods: The Caco-2 cell monolayer model was used to study the transport mechanism of Lac-NCTD and Lac-NCTD-NPs across the membranes. The relative factors for enhancing the absorption of drug carriers, including time, temperature, pH value, drug concentration, enhancers, and inhibitors, were also investigated. The differences between Lac-NCTD and Lac-NCTD-NPs in transport of membranes were explored. Results: Lac-NCTD was not only absorbed simply by active transport but also through paracellular transference as the minor. The Lac-NCTD uptake was not controlled by pH value, but positively correlated to uptake time and negatively correlated to temperature and it was also significantly enhanced by the inhibitor of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Apparent permeability coefficients (Papp) of basolateral (BL) to apical (AP) was higher than that of AP to BL. Sodium deoxycholate (SDCh) slightly enhanced the drug absorption but oxophenylarsine had no effect. Conclusion: The uptake and absorption of Lac-NCTD are active transport as the dominant process. P-gp and MRP2 have strong efflux effects on the uptake and transepithelial transport of Lac-NCTD. Lac-NCTD-NPs could significantly enhance the drug absorption compared with Lac-NCTD.