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

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 Taxoter® and non-targeted ones. Discussion: The results of this contribution showed the potential of DTX loaded FA-PF127-Chol in treatment of melanoma.