Bioactive glutathione-modified carboxymethyl cellulose hydrogels as levofloxacin delivery platforms for the Staphylococcus aureus-infected wounds management.

Bacterial infection severely impairs wound healing, and current therapeutic strategies are limited due to their poor antibacterial efficacy and potential bio-toxicity. Herein, a novel multifunctional hydrogel (CGBAgel) was fabricated with glutathione-modified carboxymethyl cellulose (CMC-GSH) and bovine serum albumin (BSA) as matrixes. Levofloxacin (LEV) was selected as an anti-bacterial agent and encapsulated in CGBAgel to fabricated LEV@CGBAgel. Studies found that LEV@CGBAgel exhibited favorable physicochemical properties, robust broad-spectrum antibacterial activity against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) strains, excellent biocompatibility, negligible cytotoxicity, and potent hemostatic and adhesive performance. In a mouse model of S. aureus-infected full-thickness skin wounds, LEV@CGBAgel achieved almost complete bacterial clearance, significantly accelerated wound closure with a closure rate of 99.9 ± 0.1% at 14 d, and promoted skin tissue regeneration. At the mechanistic level, LEV@CGBAgel mitigated local inflammation by inhibiting pro-inflammatory cytokines (TNF-α and IL-6), accelerated angiogenesis via upregulating VEGF and CD31, and promoted extracellular matrix remodeling by boosting collagen deposition. The in vivo safety evaluations confirmed that LEV@CGBAgel did not induce systemic, hematological, hepatic, and renal toxicity. Collectively, LEV@CGBAgel integrates multiple wound-healing functions with superior biosafety, holding great clinical translation potential for bacteria-infected wound management.