COX-2 targeted therapy for diabetic foot ulcers using T7-enhanced CS-PVA membranes.

ABSTRACT

Diabetic foot ulcers can lead to severe complications, including infection, gangrene, and even amputation, significantly impacting patients' quality of life. The application of anti-inflammatory compounds loaded into chitosan membranes offers targeted therapeutic effects, reducing inflammation and promoting tissue regeneration. This study evaluates the therapeutic efficacy of T7, a selective COX-2 inhibitor, incorporated into chitosan-polyvinylalcohol (CS-PVA) membranes for diabetic wound treatment. Cytotoxicity analysis showed high cell viability across various T7 concentrations, indicating minimal cytotoxicity. In silico pharmacology identified 98 potential inflammation-related targets for T7, further supported by GO and KEGG enrichment analyses. Developmental toxicity tests on zebrafish embryos indicated no significant toxicity up to 100 µM concentration. SEM and FTIR analyses confirmed the successful incorporation of T7 into the CS-PVA membrane, while XRD analysis indicated structural stability. The drug release assay demonstrated a sustained release profile, crucial for prolonged therapeutic efficacy. Antibacterial activity assays revealed significant inhibition of common pathogens. In vivo wound healing assays showed accelerated wound closure and enhanced collagen deposition, with histological and immunohistochemistry analyses supporting improved tissue architecture and reduced inflammation. Gene expression analysis confirmed reduced inflammatory markers. These findings suggest that T7-loaded CS-PVA membranes offer a promising, multifaceted approach to diabetic wound treatment, combining anti-inflammatory, antimicrobial, and collagen-promoting properties for effective wound healing.