In vitro anticancer efficacy of Metformin-loaded PLGA nanofibers towards the post-surgical therapy of lung cancer

Abstract

Metformin (MET) is an antihyperglycemic agent that has recently entered the spotlight as a promising anti-cancer agent. In this work, Poly (lactic-co-glycolic acid) (PLGA) polymer was applied to fabricate nanofibers (NFs) containing MET through the electrospinning method. The NFs were characterized for morphological features, degradation rate, and drug release profile. Besides, in response to treatment of A549 human lung adenocarcinoma cells with free MET and MET-loaded PLGA NFs, the cytotoxicity, accumulation of intracellular reactive oxygen species (ROS), and expression levels of apoptotic genes were investigated. The bead-free, smooth surface, and randomly-oriented MET-loaded electrospun NFs exhibited a relatively constant rate of degradation over the 24 days and an initial rapid drug release at first days, and a sustained discharge for more than 2-week. MET-loaded PLGA NFs displayed significant cytotoxicity on A549 lung cancer cells than free MET after 48 h. Furthermore, MET-loaded NFs were efficient to enhance the intracellular ROS levels causing apoptosis induction in the cancer cells. According to the gene expression investigations, it was uncovered that MET-loaded NFs induce a significant alteration in the expression levels of Bax and Bcl-2, caspases-3 and -9 than free MET. Overall, the findings showed anti-cancer efficiency of the MET-loaded PLGA nanofibrous scaffold signifying its potential application as an implantable drug delivery system for inhibiting the recurrence of lung cancer after surgical resection.