Repurposing ivermectin and ciprofloxacin in nanofibers for enhanced wound healing and infection control against MDR wound pathogens

Abstract

Microbial colonization is considered the most common cause of delayed or non-healing wounds, as they compete for nutrients and oxygen with healthy cells, and produce toxins that paralyze the innate capacity of wound healing. Topical application of antibiotics with wound healing promoters is preferred to control wound infections and to deliver essential growth factors. As a proof of principle, we have repurposed the anti-helminthic drug ivermectin (IVM) and antibiotic ciprofloxacin (CIP) in the fabrication of 2D electrospun composite nanofibers (NF) and analyzed their wound healing and infection control efficiency in in vitro and in ovo. The fabricated nanofibers were characterized using FTIR, SEM, and their tensile strength was also analyzed. The size of the nanofibers (CIP-IVM, CIP, IVM) ranges from 225 to 295 nm and showed higher tensile strength compared to PVA. Our composite nanofiber (CIP-IVM NF) with the concentration ranges of CIP 1.6–2.5 μg/mL and IVM 0.3–0.5 μg/mL has successfully disintegrated the biofilms of Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis infections and improved the fibroblast cell migration in in vitro wound healing model and angiogenesis in in ovo wound healing model. The CIP-IVM NF have yielded a 50 % increase in vessel length and a 60 % increase in vessel junctions in angiogenesis studies. Therefore, repurposed CIP-IVM NF has a dual role in clinical application by controlling infections caused by AMR wound pathogens and enhancing wound healing.