Combination drug delivery with actively-targeted PLGA nanoparticles to overcome multidrug resistance in breast cancer

Drug resistance is a major obstacle reducing the efficacy of cancer chemotherapy that decreases overall survival in breast cancer. P-glycoprotein (P-gp) inhibitors have potential to eliminate this problem whereas systemic usage of them such as elacridar is limited due to side effects and toxicity. This study aims to develop and evaluate paclitaxel and elacridar co-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles actively targeted to transferrin receptors to deliver anti-cancer drug and simultaneously overcome multi-drug resistance in breast cancer. In this study, PLGA nanoparticles were prepared by nanoprecipitation method and decorated with transferrin. Following characterization of the nanoparticles and drug release experiments, their efficacy was evaluated on breast cancer EMT6/AR1.0 cells which have high P-gp expression and resistance to paclitaxel. The average particle size and zeta potential of transferrin-decorated paclitaxel and elacridar co-loaded PLGA nanoparticles were 226.9 nm and - 3.9 mV, respectively. Their encapsulation efficiency was quite high (70-76%) and comparable for both paclitaxel and elacridar. Decoration with transferrin led to facilitated uptake of the nanoparticles by breast cancer cells and the combinatorial delivery of paclitaxel and elacridar through PLGA nanoparticles breached the resistance and enabled cytotoxicity. In conclusion, simultaneous and targeted delivery of nanoparticles co-loaded with P-gp inhibitors and anti-cancer drugs may be a promising approach for cancer therapy.