Background: Cabazitaxel (CTX) is a second- generation taxane derivative, a class of potent anticancer
drugs with very low water solubility. CTX is used in patients with resistant prostate cancer unresponsive to the
first generation taxane, docetaxel. Currently marketed formulations of CTX contain high concentrations of
surfactant and ethanol, which cause severe hypersensitivity reactions in patients.
Methods: In order to increase its solubility, two hemiester analogs; CTX-succinate and CTX-glutarate were
synthesized and characterized. To improve the solubility of hemiesters even more, dextran as a biocompatible
polymer was also conjugated to hemiester analogs. MTT assay was performed on MCF-7 cell line to evaluate the
cytotoxicity effect of hemiesters and conjugates.
Results: Based on the results, hemiester analogs increased water solubility of the drug up to about 3 and 8 fold.
Conjugation to dextran enhanced the CTX solubility to more than 1500 fold. These conjugates released the
conjugated CTX in less than 24 hours in a pH dependent manner and showed proper hemocompatibility
characteristics. The hemiesters had approximately similar cytotoxicity in comparison with CTX and the dextran
conjugates showed higher cytotoxicity effect on MCF-7 cell line.