Modulation of the anticancer activities of paclitaxel by Cremophor micelles

The objective of this study was to determine the effect of Cremophor (CrEL) on the antineoplastic effect induced by paclitaxel (PTX). Fluorescence spectroscopy, employing pyrene as a probe, was used to determine the critical micelle concentration (CMC) of CrEL. EL4 murine thymoma cells and MDA-MB-231 human breast cancer cells were treated with PTX in different concentrations of CrEL. G2 arrest with 8 N polyploidy was observed in PTX-treated EL4 cells but not in MDA-MB-231 cells. Cell cycle analysis via propidium iodide (PI) staining showed that the frequency of G2 arrest decreased as the CrEL concentration exceeded 0.02% (w/v), demonstrating the effect of CrEL micelle formation on the antimitotic activity of PTX. CrEL was also shown to enhance PTX-induced cell death in vitro by Annexin V/PI staining. Treatment of C57BL/6 mice with PTX in a lower concentration of CrEL resulted in higher myelosuppression, decreased both Ki-67 expression and survival rate, suggesting that CrEL micelle formation above the CMC may lower the cytotoxic activity of PTX in vivo. The data obtained in this study demonstrate CrEL micelle-mediated modulation of the cell cycle and cell death induced by PTX in vitro and the antineoplastic efficacy of PTX in vivo.