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Synthesis and in vitro assessment of novel water‐soluble dextran‐docetaxel conjugates as potential p H sensitive system for tumor‐targeted delivery
Author(s) -
Parhizkar Elahehnaz,
Daneshamouz Saeid,
MohammadiSamani Soliman,
Sakhteman Amirhossein,
Parhizkar Golnaz,
Omidi Mahmoud,
Ahmadi Fatemeh
Publication year - 2017
Publication title -
journal of applied polymer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.575
H-Index - 166
eISSN - 1097-4628
pISSN - 0021-8995
DOI - 10.1002/app.45457
Subject(s) - dextran , docetaxel , conjugate , solubility , chemistry , cytotoxicity , conjugated system , drug delivery , combinatorial chemistry , chromatography , organic chemistry , in vitro , biochemistry , polymer , medicine , chemotherapy , surgery , mathematical analysis , mathematics
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.