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 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.

Antimicrobial peptides-loaded smart chitosan hydrogel: Release behavior and antibacterial potential against antibiotic resistant clinical isolates.

In this study, we synthesized thermo-responsive chitosan (TCTS) hydrogels, and loaded with different concentrations of antimicrobial peptide (AMP) (0, 4, 8 and 16 µg·ml-1) to fabricate an antibacterial wound dressing against resistant clinical isolates. Physico-chemical properties, release behavior, cytobiocompatibility and antibacterial activity of the AMP-TCTS hydrogels against standard strain and resistant Acinetobacter baumannii were fully determined in vitro. The TCTS-40% ß-glycerolphosphate hydrogels showed a gelation time of 15 min at 37 °C. 80% weight loss at day 35 with no changes in pH value was observed. AMP-TCTS hydrogels showed a burst release of AMP (around 40%) at day 1, and a controlled release up to day 7. A dramatic water uptake was observed at first 4 h, and then continued for 10 h in a steady manner. All the AMP-TCTS hydrogels showed excellent cytobiocompatibility for human fibroblasts. The TCTS showed no antibacterial activity against both standard strain and clinical isolates. All the AMP-TCTS hydrogels had strong antibacterial activity against standard strains, but only 16 µg·ml-1 showed antibacterial behavior against resistant A. baumannii. Our results strongly suggest the 16 µg·ml-1 AMP-TCTS hydrogel as an excellent antibacterial wound dressing against resistant A. baumannii, and now promises to proceed with pre-clinical investigations.