Co-encapsulation of paclitaxel and baicalein in nanoemulsions to overcome multidrug resistance via oxidative stress augmentation and P-glycoprotein inhibition

Multidrug resistance (MDR) is a major obstacle for clinical application of paclitaxel (PTX). Recent studies have suggested that baicalein (BA) might be a potent MDR reversal agent with the ability of P-glycoprotein inhibition and oxidative stress augmentation. Herein, we co-encapsulated PTX and BA in nanoemulsions (PTX/BA NE) for overcoming MDR in breast cancer. Paclitaxel-cholesterol complex and baicalein-phospholipid complex were prepared to improve the liposolubility of PTX and BA. The cytotoxicity of the combination of PTX and BA with different weight ratios were evaluated and the combination with a weight ratio of 1/1 exhibited the strongest synergistic effect. In vitro cytotoxicity study indicated that PTX/BA NE had a better antitumor efficacy in MCF-7/Tax cells than other PTX formulations. Studies on cellular uptake demonstrated that the PTX/BA NE could effectively accumulate in cancer cells. Mechanism research showed that PTX/BA NE could significantly increase the cellular reactive oxygen species (ROS), decrease cellular glutathione (GSH), and enhance caspase-3 activity in MCF-7/Tax cells. More importantly, in vivo antitumor study demonstrated that PTX/BA NE exhibited a much higher antitumor efficacy than other PTX formulations. These findings suggest that co-delivery of PTX and BA in nanoemulsions might provide us a potential combined therapeutic strategy for overcoming MDR.

Scheme 1. Schematic illustration of co-delivery of PTX and BA via nanoemulsions (PTX/BA NE) to overcome MDR in MCF-7/Tax cells. Nanoemulsions can efficiently deliver the therapeutic agents to the tumor cells through typical endocytosis pathway. PTX/BA NE significantly increase the cellular reactive oxygen species (ROS), reduce the cellular glutathione (GSH), and enhance caspase-3 activity in MCF-7/Tax cells, eventually resulting in apoptosis.Figure optionsDownload high-quality image (153 K)Download as PowerPoint slide