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

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

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 11 , 2017

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Graphical 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.

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

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Article Details

Year: 2017
Published on: 24 November, 2017
Page: [1555 - 1562]
Pages: 8
DOI: 10.2174/1871520617666170213120506
Price: $65

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