title: Synthesis and Characterization of Water-soluble Conjugates of Cabazitaxel Hemiesters-Dextran.
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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Elahehnaz
authors.initials: E
authors.lastname: Parhizkar
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.|Research Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ahmadi
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Saeid
authors.initials: S
authors.lastname: Daneshamouz
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.|Research Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Soliman
authors.initials: S
authors.lastname: Mohammadi-Samani
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sakhteman
authors.affiliation: Department of Chemistry, University of Isfahan, Isfahan 81746-73441, Iran.
authors.forename: Golnaz
authors.initials: G
authors.lastname: Parhizkar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D061986:MCF-7 Cells; D015394:Molecular Structure; D012995:Solubility; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000737:chemistry* / Q000494:pharmacology*; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D043823:Taxoids; D014867:Water; C552428:cabazitaxel
keywords: Cabazitaxel; dextran conjugates; drugs.; hemiesters; pH stability; water solubility