Multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery to overcome drug resistance in tumor treatment

A facile self-assembly strategy to fabricate vitamin E-tocopheryl polyethylene glycol succinate(TPGS) based nanoparticles with a high drug loading level for co-delivery of multiple drugs was developed. To overcome multi-drug resistance, a chemotherapeutic agent(paclitaxel, PTX) and a drug resistance inhibitor(tariquidar, TQR) were co-loaded in the vitamin E-TPGS based nanoparticle to obtain TPGS/PTX/TQR nanoparticles. The sizes of mono-drug loaded TPGS/PTX nanoparticles and dual-drug loaded TPGS/PTX/TQR nanoparticles were below 150 nm with relatively narrow size distributions.The efficiencies of the drug delivery systems on tumor cells inhibition and reversal of drug resistance were evaluated in drug resistant cancer cells(MCF-7/ADR) as compared with nonresistant cells(He La). Due to the effective inhibition of the P-gp efflux by TQR, the dual-drug loaded nanoparticles exhibited significantly improved tumor cell inhibitory efficiency. To study the immunostimulatory effect, the effect of the drug delivery system on the production of IL-10, a cytokine related to tumor development, in the drug resistant cells was determined. After the treatment by the drug delivery systems, the concentration of IL-10 in the cell supernatant decreased. The multi-drug loaded vitamin E-TPGS nanoparticles for synergistic drug delivery have promising applications in reversal of drug resistance in tumor treatments.