Plasma mediated immobilization of metformin on polyethylene: effects on drug release, antibacterial activity, and biocompatibility

Abstract

Metformin, a widely used antidiabetic drug, has gained attention for its potential applications in antimicrobial surfaces, delivery systems, and anticancer therapy. However, immobilizing metformin in a stable, bioactive, and dose-controllable manner onto a chemically inert, hydrophobic surface is challenging. The objective of this study is to immobilize metformin at various concentration (0.5, 1, 2, 5, 10, and 20 g·L−1) onto low-density polyethylene (LDPE) surfaces by a multistep approach with the aim of creating bioactive coatings. In this approach, LDPE was first treated with a 40 kHz low pressure plasma discharge in air atmosphere, followed by non-covalent attachment of acrylic acid via a grafting technique. Metformin was covalently attached to the surface via N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC) and N-Hydroxysuccinimide (NHS) activation, while its presence on the polymer surface was confirmed by Water contact angle (WCA), Fourier transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). Sustained metformin release with a shift from Fickian to first-order kinetics was observed at higher drug loading. Antibacterial testing against Staphylococcus aureus and Escherichia coli showed no antibacterial effect at the selected concentration levels. Cytocompatibility assays with multipotent mesenchymal cells showed good biocompatibility of modified surfaces, with only dose-dependent cytotoxicity at higher metformin concentrations (>5 g·L−1). These results demonstrate that despite the absence of antibacterial effects, the developed system offers a promising platform for further biomedical applications requiring controlled drug surface functionalization and retained cytocompatibility.