Synergetic dual antibiotics-loaded chitosan/poly (vinyl alcohol) nanofibers with sustained antibacterial delivery for treatment of XDR bacteria-infected wounds

Resistance of bacterial pathogens to conventional antibiotics has remained a significant challenge in managing post-wound infections, especially in developing countries. Here, a nanofibrous chitosan/poly (vinyl alcohol) (CS/ PVA) mat was designed for controlled delivery of three different concentrations of two antibiotics (colistin/ meropenem ratio of 32/64 mu g/ml (AB1), 64/128 mu g/ml (AB2), and 128/256 (AB3) mu g/ml) with synergistic antibacterial activity against ATCC and extensively drug-resistant (XDR) Acinetobacter baumannii clinical isolates. The scaffolds showed a uniform fibrous structure with no bead formation with a sustained release of the anti-biotics for one week. The elongation at break, wettability, porosity, and average fiber diameter decreased with increased antibiotics concentrations. Young's modulus and tensile strength showed a significant increase after adding antibiotics. All the constructs showed excellent in vitro cytocompatibility for fibroblasts and biocom-patibility in an animal model. The antibacterial assays confirmed the dose-dependent antibacterial activity of the CS/PVA. The scaffolds loaded with AB2 and AB3 showed biocidal properties against ATCC, while only CS/PVA/ AB3 had antibacterial activity against XDR clinical isolates. This study suggests the CS/PVA/AB3 nanofibrous scaffold contained 128/256 mu g/ml colistin/meropenem as an excellent antibacterial wound dressing for pro-tection of skin wounds from XDR clinical isolates and now promises to proceed with pre-clinical investigations.