A novel ursodeoxycholic acid–chitosan-folate conjugates for the delivery of calcitriol for cancer therapy

The primary drawback of calcitriol (CAL) as an anticancer drug is its induction of hypercalcemia and hyperphosphatemia. Thus, there is an urgent need for the development of targeted delivery systems for improving the safety and efficacy of CAL. In this study, the modification of chitosan was carried out with ursodeoxycholic acid and covalently interacted with folic acid for developing a novel tumor-targeting drug delivery system. The conjugates were structurally characterized via X-ray diffraction, 1H NMR, and Fourier-transform infrared spectroscopy. Fluorescence spectroscopy and zeta potential measurements were used for analyzing the physical as well as chemical properties of the self-aggregates in an aqueous medium. Transmission electron microscopy was carried out for visualizing the surface morphology of self-aggregates. The drug-loading and encapsulation efficiencies and in vitro drug release of the prepared CAL-loaded micelles were further evaluated. MTT assay revealed that the cytotoxicity of folate-micellar CAL (UDCA–CS–FA/CAL) toward mice hepatocellular carcinoma cells was elevated relative to that of micelles without folate or free CAL. The growth of the tumour was significantly attenuated by UDCA–CS–FA/CAL micelles in a xenograft tumorigenesis model. Quantification of serological indicators in UDCA–CS–FA/CAL-treated and control mice showed that CAL-loaded UDCA–CS–FA could be a solution to the side effects of CAL. In conclusion, the UDCA–CS–FA/CAL micelles can be used as an effective approach for CAL-based targeted and safe chemotherapy.