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

• Published in: International journal of biological macromolecules 2023-02, Vol.229, p.22-34
• Main Authors: Alizadeh, Sanaz, Farshi, Paniz, Farahmandian, Navid, Ahovan, Zahra Aliakbar, Hashemi, Ali, Majidi, Mohammad, Azadbakht, Abdolnaser, Darestanifarahani, Mahsa, Sepehr, Koushan Sineh, Kundu, Subhas C., Gholipourmalekabadi, Mazaher
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial wound dressing; Bacteria; Chitosan; Chitosan - chemistry; Colistin; Electrospinning; Meropenem; Nanofibers - chemistry; Polyvinyl Alcohol - chemistry; Post-wound infection; Resistant bacteria
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2022.11.288

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. [Display omitted] •Optimization of synergistic antibiotics-loaded CS/PVA nanofibrous mat•Optimization of dual (colistin-meropenem) antibiotics release behavior•Optimization of antibacterial activity against drug resistant bacteria•In vitro and in vivo biocompatibility of antibacterial CS/PVA nanofibers•Optimal meropenem/colistin- loaded CS/PVA is suitable for infected wounds therapy.