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

Int J Biol Macromol. 2023 Feb 28:229:22-34. doi: 10.1016/j.ijbiomac.2022.11.288. Epub 2022 Nov 29.

Abstract

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 μg/ml (AB1), 64/128 μg/ml (AB2), and 128/256 (AB3) μg/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 antibiotics 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 biocompatibility 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 μg/ml colistin/meropenem as an excellent antibacterial wound dressing for protection of skin wounds from XDR clinical isolates and now promises to proceed with pre-clinical investigations.

Keywords: Antibacterial wound dressing; Chitosan; Electrospinning; Post-wound infection; Resistant bacteria.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacteria
  • Chitosan* / chemistry
  • Colistin
  • Meropenem
  • Nanofibers* / chemistry
  • Polyvinyl Alcohol / chemistry

Substances

  • Anti-Bacterial Agents
  • Chitosan
  • Meropenem
  • Colistin
  • Polyvinyl Alcohol