Paclitaxel and curcumin co-loaded mixed micelles: Improving in vitro efficacy and reducing toxicity against Abraxane®

Abstract

Paclitaxel (PTX) is one of the most effective antineoplastic drugs employed for breast and ovarian cancer therapy. However, the neurotoxicity associated with PTX administration represents one of its main drawbacks reducing patient life quality. Recently, curcumin (CUR) has been explored as a neuroprotective agent due to its antioxidant properties. Then, the co-encapsulation of PTX and CUR in a mixed micellar formulation could promote a neuroprotective effect of the micellar system and optimize breast and ovarian cancer therapy. PTX-CUR-loaded Soluplus:TPGS mixed micelles were developed and characterized by nuclear magnetic resonance, scattering techniques and transmission electron microscopy. In vitro cytotoxicity was evaluated in MDA-MB-231 and SKOV-3 cancer cells. The in vitro antioxidant performance of CUR-loaded nanoformulations was confirmed employing lipid peroxidation inhibition and DPPH colorimetric assays. The neuroprotective effect of the micellar formulations was evaluated on zebrafish larvae. Mixed micelles demonstrated an excellent colloidal stability, before and after freeze-drying. Nanoformulations with both drugs demonstrated the best in vitro anticancer performance versus the commercially available nanoformulation Abraxane® in breast and ovarian cancer cells lines. The in vitro antioxidant properties of the mixed micelles with CUR were confirmed and their in vivo potential neuroprotective effect was assessed in the zebrafish model.