LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Enhanced Liver Targeting of Camptothecin via Conjugation with Deoxycholic Acid

Photo by jnnfrchn from unsplash

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… Click to show full abstract

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 (G2). 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 G2 and CPT were assessed in 2D and 3D HepG2 cell models. The stability of G2 and CPT was evaluated in vitro (in simulated gastric fluid, simulated intestinal fluid, and fresh rat plasma). Finally, biodistribution of G2 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 G2 in HepG2 cells, but had no distinct effects on CPT. Meanwhile, G2 exhibited better stability compared with CPT. More importantly, biodistribution study in mice demonstrated that the liver targeting index of G2 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.

Keywords: liver targeting; cpt; camptothecin; deoxycholic acid; conjugation deoxycholic; acid

Journal Title: Molecules
Year Published: 2019

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.