Overcoming cytotoxicity of antibiotics by 2-deoxy-d-ribose: A dual-functional antibiotic and angiogenic hydrogel for potential healing of infected wounds.

Antibiotic-induced cytotoxicity continues to be a key limitation in the clinical management of chronic infected wounds, often impairing tissue regeneration and delaying wound closure. The present study demonstrates that 2-deoxy-d-ribose (2dDR), a known angiogenesis stimulant, significantly improves cytocompatibility when co-administered with the key antibiotic ciprofloxacin. This beneficial effect of 2dDR toward ciprofloxacin did not extend to ofloxacin to any useful extent and not at all to silver sulfadiazine. Leveraging this finding of the study, we formulated a novel sodium alginate-collagen-based hydrogel co-loaded with ciprofloxacin and 2dDR (Gel-CIP/2dDR). FTIR spectroscopy confirmed the structural integrity of the hydrogel, and in vitro, drug release profiles revealed sustained delivery of both ciprofloxacin and 2dDR over the period of 168 and 120 h, respectively. In vitro cell studies confirmed the hydrogel's cytocompatibility with NIH 3 T3 fibroblasts up to 72 h. Antibacterial testing showed robust efficacy against both Gram-negative (E. coli, P. aeruginosa) and Gram-positive (S. aureus, MRSA) pathogens. An in ovo chick chorioallantoic membrane (CAM) assay validated the neovascularization ability of Gel-CIP/2dDR. In a full thickness cutaneous rat wound model, wounds treated with Gel-CIP/2dDR showed 87.5% wound closure compared to 72.83% healing in control group in 17 days. Histological analysis also showed enhanced angiogenesis, reduced inflammation, stimulated re-epithelialization, and augmented collagen deposition indicating good wound healing by the hydrogel. Collectively, Gel-CIP/2dDR is a therapeutic strategy that overcomes the cytotoxicity of an antibacterial drug with its proangiogenic ability and ensures strong potential for treating chronic and infected wounds.