The effects Metformin/Irinotecan-loaded PLGA nanoparticles on glutamate re-uptake time and alteration EAAT1 gene expression level in vitro

Abstract

Objective(s): The present study was designed to evaluate of Metformin/Irinotecan-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) effects on glutamate re-uptake time and receptor expression status in both glioblastoma multiforme (GBM) and cortex neuron cultures. The study was performed on glioblastoma cell line and primer cortex neuron.Materials and Methods: The re-uptake time and gene expression status of pure drugs and MET- or IRI-loaded-PLGA NPs on healthy neuron cells and U-87 MG cell line were investigated by using glutamate specific voltammetry electrodes technique and real time PCR. Results: Both MET and MET-PLGA NPs (1 and 2 mM) exhibited significant cytotoxicity on both U87MG and neuron cells. MET and MET-PLGA NPs (0.5 mM) showed lower cytotoxic effects on both cells. IRI and IRI-PLGA NPs (100 µM) had significant cytotoxic effects on both cell lines. Conclusion: All drug-loaded NPs caused a significant reduction in glutamate reuptake time compared with free drugs, blank NPs and cancer cells control groups. Consequently, MET- and IRI-loaded PLGA NPs may be a promising approach to treat GBM.

Keywords

• EAAT1
• Irinotecan
• Metformin
• PLGA
• Voltammetry