Enhancing wound healing with synergistic dual-drug electrospun roflumilast and L-arginine loaded PLA/PVA nanofibers through fabrication, optimization, and in vivo assessment

Abstract

Current trends in improved wound management emphasize the development of dual-drug-loaded electrospun nanofibrous scaffolds. Herein, electrospun dual-drug loaded PLA/PVA nanofibrous scaffolds, incorporating roflumilast, a selective phosphodiesterase-4 inhibitor with anti-inflammatory activity, and L-arginine, a precursor to nitric oxide with stimulating activity towards wound healing and tissue regeneration, were developed. A dual-spinneret electrospinning process enabled the co-loading of drugs in PLA and PVA phases. Scaffolds were characterized by SEM, FTIR, and XRD, showing consistent fiber morphology, and amorphous drug formation. FTIR analysis was performed to confirm drug-polymer compatibility and successful incorporation of roflumilast and L-arginine within the PLA/PVA nanofibrous matrix. Swelling ratio analysis indicated controlled hydration behavior regarding polymer-drug composition, and dual-drug-loaded fibers exhibited maximum initial swelling (610%) and stabilization at ~ 240%. In vivo rat excision wound healing model showed that the dual-drug loaded nanofibers demonstrated enhanced wound healing with ~ 99.8% healing on day 14, which was significantly better, compared to nanofibers incorporating a single drug and control groups. Moreover, histological studies revealed the absence of residual granulation tissue and enhanced re-epithelialization in the dual-drug treated group. These results indicate that roflumilast and L-arginine co-loaded PLA/PVA nanofibers exhibit wound-healing and regenerative properties, offering a promising therapeutic platform for enhanced wound repair.