3 years ago

Synthesis and in vitro assessment of novel water-soluble dextran-docetaxel conjugates as potential pH sensitive system for tumor-targeted delivery

Synthesis and in vitro assessment of novel water-soluble dextran-docetaxel conjugates as potential pH sensitive system for tumor-targeted delivery
Mahmoud Omidi, Amirhossein Sakhteman, Golnaz Parhizkar, Elahehnaz Parhizkar, Fatemeh Ahmadi, Soliman Mohammadi-Samani, Saeid Daneshamouz
Docetaxel is a potent taxane agent mostly used in breast, lung, and prostate cancers. Its low water solubility is the major drawback that leads to use of Tween 80 as surfactant and ethanol as solvent in market formulation. But, these excipients cause severe hypersensitivity reactions. In this study, docetaxel was conjugated to biocompatible polymer, dextran 70 kDa, via a pH sensitive linker to enhance solubility and diminish the need of surfactants. Folic acid was also conjugated to dextran to provide targeted delivery. Synthesized conjugates were examined for solubility, hemo-compatibility, stability, and cytotoxicity on MCF-7 and MDA-MB-231 cell lines. Results showed about 1200-fold enhancement in water solubility by dextran and 280-fold by dextran-folate conjugation. Conjugates released the drug in a pH-dependent manner and faster hydrolysis was observed in pH 5.4 than physiological pH 7.4. Docetaxel-dextran conjugates showed proper hemo-compatibility and presented greater cytotoxicity than docetaxel solution. Higher cytotoxicity was seen in folate conjugated samples and the final conjugates targeted by folate would be suitable novel substitutions for currently marketed formulation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45457.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/app.45457

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