Metformin and Silibinin co-loaded PLGA-PEG nanoparticles for effective combination therapy against human breast cancer cells

Abstract Polymeric nanoparticle (NP) mediated combination chemotherapy has been proposed to be an efficient strategy for cancer treatment via exerting synergism among the different drugs, suppressing drug resistance, and enhancing pharmacokinetics of the drugs which leads to a decrease in the side effects of the drug payloads. The present study examines the synergistic anticancer efficiency of two natural-based anticancer agents, Metformin (MET) and Silibinin (SIL) co-loaded PLGA-PEG NPs against T47D breast cancer cells. The resultant drug-loaded PLGA-PEG NPs displayed a spherical morphology with the uniform nanosize distribution. For both drugs, burst discharge occurred in the first 8 h, followed by sustained release over 7 days. According to MTT assay and median-effect analysis, MET/SIL-loaded PLGA-PEG NPs exhibited the most synergistic cytotoxic effect against the breast cancer cells. Besides, it was revealed that the dual drug-loaded NPs could significantly alter the expression levels of Bax, Bcl-2, caspase 3 and 9, and hTERT compared to the free combination of the drugs as well as the single drug-loaded NPs. Taken together, this work revealed that MET/SIL-loaded PLGA-PEG NP based combination therapy might have a significant potential to improve the efficiency of breast cancer therapy.