Metformin-Loaded Nanostructured Plga: A New Strategy for Enhancing Efficacy of Metformin in Breast Cancer Treatment

Abstract

Objective: Nano-formulation approaches would be more efficient in decreasing drug toxicity, preventing tumor development in relation to free form of drug.Methods: Therefore, the purpose of this study is to construct poly lactic-coglycolic acid (PLGA) nanoparticles (NPs) loaded with Metformin (MET) to investigate their cytotoxicity as well as their impact on expression levels of apoptosis related genes in MDA-MB-231 breast cancer cells. Field Emission Scanning Electron Microscope (FE-SEM) and Fourier-transform infrared spectroscopy (FTIR) characterized the synthesized NPs. Then, MTT assay was used to evaluate and compare the cytotoxic effect of various concentrations of the chemotherapeutic molecules in pure and nano-formulated forms after 48 h exposure time. Moreover, the mRNA levels of apoptosis related genes expression were studied by quantitative PCR.Results: By encapsulating MET into PLGA, the cytotoxic efficiency of the compounds considerably augmented for all concentrations. Furthermore, the results demonstrated that MET-loaded NPs could induce apoptosis in MDA-MB-231 breast cancer cell by upregulation of caspase-3, caspase-7 and BAX, along with Bcl-XL, hTERT and Cyclin D1 down regulation.

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR Signaling Pathways

“…To enhance the efficacy of MET in cancer therapy, researchers have been exploring various combination therapies. For example, a recent study has illustrated that combining MET with nanostructured poly lactic-coglycolic acid (PLGA) can improve its effectiveness in treating breast cancer [164]. Additionally, Han et al have shown that concurrent administration of MET with EGFR-TKIs can lead to better clinical results and delay the onset of EGFR-TKI resistance in non-small cell lung cancer patients.…”

Effects of metformin on cancers in experimental and clinical studies: Focusing on autophagy and AMPK/mTOR signaling pathways

“…For example, a recent study has illustrated that combining MET with nanostructured poly lactic-coglycolic acid (PLGA) can improve its effectiveness in treating BC. 181 treatments for patients in the future. 184 Additionally, Autophagy is a resistance mechanism that limits the effectiveness of enzalutamide, a small molecule used to treat castrationresistant prostate cancer.…”

“…To enhance the efficacy of MET in cancer therapy, researchers have been exploring various combination therapies. For example, a recent study has illustrated that combining MET with nanostructured poly lactic‐coglycolic acid (PLGA) can improve its effectiveness in treating BC 181 . Additionally, Han et al have shown that concurrent administration of MET with EGFR‐TKIs can lead to better clinical results and delay the onset of EGFR‐TKI resistance in non‐small cell lung cancer patients.…”