Bioactive glutathione-modified carboxymethyl cellulose hydrogels as levofloxacin delivery platforms for the...

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 (CGBA^gel) 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 CGBA^gel to fabricated LEV@CGBA^gel. Studies found that LEV@CGBA^gel 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@CGBA^gel 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@CGBA^gel 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@CGBA^gel did not induce systemic, hematological, hepatic, and renal toxicity. Collectively, LEV@CGBA^gel integrates multiple wound-healing functions with superior biosafety, holding great clinical translation potential for bacteria-infected wound management.