Clarithromycin as a macrolide antibiotic and zinc oxide (ZnO) nanoparticles with antibacterial and anti-inflammatory properties was incorporated into the chitosan/gelatin/polyurethane (PU) core–shell nanofibers prepared by the coaxial electrospinning method. The morphology and structure of nanofibers were characterized using SEM, FTIR, water contact angle, degradation rate, and swelling tests. The mean fiber diameters of the chitosan/gelatin/PU (CGP), CGP containing 1000 μM clarithromycin, CGP containing 2000 μM clarithromycin, CGP containing 0.5% ZnO, CGP containing 1 wt% ZnO, CGP containing 1000 μM clarithromycin, and 0.5 wt% ZnO and CGP containing 2000 μM clarithromycin, and 1 wt% ZnO were 210 ± 110 nm, 235 ± 100 nm, 250 ± 120 nm, 300 ± 120 nm, 360 ± 130 nm, 410 ± 130 nm, and 460 ± 140 nm, respectively. The gradual faster release of ZnO nanoparticles from core–shell nanofibers was obtained within 24 h; whereas, the sustained release of clarithromycin was achieved during 120 h. Loading of clarithromycin and ZnO nanoparticles into the nanofibers resulted in 100% bactericidal activity of core–shell nanofibers against both Escherichia coli and Staphylococcus aureus. The cell viability results indicated that loading of 0.5 wt% ZnO nanoparticles and 2000 μM clarithromycin was suitable for the development of the synthesized core–shell nanofibers as a potential wound dressing.
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