Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran

Title:Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran

Volume: 17 Issue: 11

Author(s): Elahehnaz Parhizkar, Fatemeh Ahmadi*, Saeid Daneshamouz, Soliman Mohammadi-Samani, Amirhossein Sakhteman and Golnaz Parhizkar

Affiliation:

• Department of Pharmaceutics, Faculty of Pharmacy, Shiraz University of Medical Sciences, P.O. Box: 71468-64685, Shiraz,Iran

Keywords: Cabazitaxel, dextran conjugates, hemiesters, pH stability, water solubility, drugs.

Abstract: 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.

Cite this article as:

Parhizkar Elahehnaz, Ahmadi Fatemeh*, Daneshamouz Saeid, Mohammadi-Samani Soliman, Sakhteman Amirhossein and Parhizkar Golnaz, Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran, Anti-Cancer Agents in Medicinal Chemistry 2017; 17 (11) . https://dx.doi.org/10.2174/1871520617666170213120506