| Summary: | Camptothecin (CPT) shows potent anticancer activity through inhibition of topoisomerase I. However, its water insolubility and severe toxicity limit its clinical application. Coupling with bile acid moieties is a promising method for liver-targeted drug delivery, which takes advantage of the bile acid receptors on hepatocytes. In this study, we evaluated the potential liver targeting and stability of a deoxycholic acid-CPT conjugate (<b>G2</b>). The competitive inhibition of antitumor activity experiment based on bile acid transporters was performed using the MTT method. The effects of deoxycholic acid on uptake of <b>G2</b> and CPT were assessed in 2D and 3D HepG2 cell models. The stability of <b>G2</b> and CPT was evaluated in vitro (in simulated gastric fluid, simulated intestinal fluid, and fresh rat plasma). Finally, biodistribution of <b>G2</b> and CPT was investigated in Kunming mice following oral administration. The results showed that deoxycholic acid pretreatment could significantly reduce the antitumor activity and cellular uptake of <b>G2</b> in HepG2 cells, but had no distinct effects on CPT. Meanwhile, <b>G2</b> exhibited better stability compared with CPT. More importantly, biodistribution study in mice demonstrated that the liver targeting index of <b>G2</b> increased 1.67-fold than that of CPT. Overall, the study suggests that conjugation with deoxycholic acid is a feasible method to achieve liver targeting delivery of CPT.
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