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Pharmacokinetics, Organ Toxicity and Antitumor Activity of Docetaxel Loaded in Folate Targeted Cholesterol Based Micelles Publisher Pubmed



Taymouri S1 ; Varshosaz J1 ; Hassanzadeh F2 ; Javanmard SH3 ; Mahzouni P4
Authors
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Authors Affiliations
  1. 1. Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Physiology Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Current Drug Delivery Published:2016


Abstract

Background: To overcome insufficient concentration of chemotherapeutic drugs at tumor site and severe side effects in non-targeted tissues which limit their use targeting their overexpressed receptors represent a promising approach for cancer therapy. Methods: The antitumor activity of docetaxel (DTX) loaded in folate targeted Synpronic F127-Cholesterol (FA-PF127-Chol) nanomicelles was evaluated in C57BL6 mice bearing melanoma and their survival was studied. The pharmacokinetic of DTX loaded FA-PF127-Chol micelles in comparison with Taxoter® was investigated in male Wistar rats. The tumor proliferation was detected by Ki67 assay. The systemic organ toxicity was evaluated in healthy bulb-c mice. Results: DTX loaded FA-PF127-Chol micelles significantly inhibited tumor growth and enhanced animal survival compared to Taxoter® and non-targeted micelles. FA-PF127-Chol micelles significantly enhanced mean residence time (MRT) and AUC0-∞of DTX compared to Taxoter®. The immunehistochemical study demonstrated that DTX loaded FA-PF127-Chol significantly inhibited intra-tumoral cell proliferation in comparison with other treated groups. Safety evaluation showed no toxicity of DTX loaded targeted micelles on blood cells. Histopathology analysis of major organs of mice treated with DTX loaded FA-PF127-Chol micelles showed less tissue damages compared to TaxoterR and non-targeted ones. Discussion: The results of this contribution showed the potential of DTX loaded FA-PF127-Chol in treatment of melanoma. © 2016 Bentham Science Publishers.
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