Human ABCC3 Stable Cell Line - MDCK

Pharmaceutical excipient PEG400 is a common component of traditional Chinese medicine compound preparations. Studies have demonstrated that pharmaceutical excipients can directly or indirectly influence the disposition of active pharmaceutical ingredients within the body, thereby affecting their bioavailability. To elucidate the impact of PEG400 on the pharmacokinetics of baicalin within hepatocytes-as well as the underlying mechanisms-researchers first investigated the effects of PEG400 on the metabolic disposition of baicalin at the cellular level. Subsequently, Western blot analysis was employed to assess the influence of PEG400 on the protein expression levels of baicalin-associated transporters (BCRP, MRP2, and MRP3). Furthermore, interactions between PEG400 and these transporters were investigated using MDCKII cell monolayer models (specifically MDCKII-BCRP, MDCKII-MRP2, and MDCKII-MRP3), in conjunction with membrane vesicles overexpressing the specific transporters (BCRP, MRP2, and MRP3) and supplemented with transporter-specific inhibitors; this approach aimed to explore the potential mechanisms of action. The results revealed that PEG400 significantly influenced the intracellular concentration of baicalin within hepatocytes. Further experiments utilizing vesicle transport assays and MDCKII cell models demonstrated a significant reduction in the efflux rate of baicalin, suggesting that PEG400 exerts a potent inhibitory effect on the corresponding transporters. In summary, PEG400 modulates the metabolic disposition of baicalin within the liver by influencing efflux transporters, thereby enhancing the bioavailability of baicalin to a certain extent.

MRP3 (ABCC3) is localized to the basolateral membrane of cells and facilitates the efflux of drugs across this membrane. In the MDCK II-MRP3 cell model, the ratio of Papp_AP-BL to Papp_BL-AP for baicalin was elevated; this indicates that MRP3 promotes the transport of baicalin toward the basolateral side, thereby facilitating the drug's entry into the bloodstream. In this MDCK II-MRP3 cell model, the Papp_AP-BL/Papp_BL-AP ratio in the high-concentration group was 3.76 ± 0.81, which was significantly higher than the 0.63 ± 0.37 observed in the control group (Figure 1b)-representing a 5.97-fold increase in this ratio. This result suggests that PEG400 significantly activated the transport process of baicalin.

Figure 1. The effect of PEG400 on transepithelial transport of baicalin from AP to BL side and BL to AP side across MDCK II-MRP3 cell monolayer. (Yang D, et al., 2024)