Synthesis and Characterization of New Liver Targeting 5‐Fluorouracil‐Cholic Acid Conjugates

The objective of this work was to develop a liver-specific antihepato carcinoma agent. A series of 5-fluorouracil / cholic acid conjugates (5-FU-cholic acid conjugates) were prepared and tested for their chemical characteristics and bio-distribution properties. The in-vitro stability trial showed 5-FU-cholic acid conjugates could be completely hydrolyzed by heating at 70 degrees C in an acidic solution, pH = 1, for 5 min. The fast and complete hydrolysis of these compounds could be compatible with a fast separation and analysis method to shorten the analysis time. The decomposition speeds of the 5-FU-cholic acid conjugates in different organs of mice at several time points after oral administration were evaluated by measuring the concentrations of regenerated 5-FU in organ tissue. The results were compared with those of the controls, which was a group of mice orally taking 5-FU. The concentrations of 5-FU in mice liver tissue were remarkably increased after oral administration of the prodrugs, and were much larger than if only orally administered 5-FU. The results suggested the feasibility to improve therapeutic efficiency of liver targeting treatments by using cholic acid as the vector of drugs.