Sprayable ciprofloxacin loaded chitosan nanospheres-based topical formulation for eliminating multidrug-resistant bacteria and accelerating infected wound healing.

Multidrug-resistant (MDR) bacteria represent a formidable global health crisis with a substantial risk of prolonged infections due to the diminishing efficacy of traditional antibiotic therapies against these resilient pathogens. A dual strategy offering rapid inactivation of MDR bacteria and reduction in wound area could effectively promote wound healing. In this work, we developed a sprayable topical formulation by integrating a biocompatible biopolymer chitosan with a chemotherapeutic drug ciprofloxacin. The as-developed ciprofloxacin-loaded chitosan nanospheres (CIP-CNSs) exhibited a high encapsulation efficiency (70 %) and robust in vitro antibacterial activity against different MDR strains such as E. coli, S. aureus, and P. aeruginosa. However, CIP-CNSs did not induce any adverse side effects either in vitro or topically on the skin as confirmed by cytotoxicity assay and acute dermal irritation test. Moreover, in albino rabbits wound model, CIP-CNSs significantly accelerated wound healing with a wound closure rates of 75-85 %, within the first-week of post-incision, as compared to a commercial ointment. Furthermore, histopathological staining confirmed faster re-epithelialization and collagen deposition in wounded regions, without any hemorrhage or tissue infection. This study underscores the potential of CIP-CNSs topical formulation as a viable therapeutic strategy against the burgeoning threat of MDR-associated wound infections.