Diabetic foot wounds (DFUs) are counted as one of the most common microvascular complications associated with poorly controlled and chronic diabetes mellitus. It confers a serious challenge to clinical practice, surmounting hyperglycemia-induced disturbance in angiogenesis and endothelial dysfunction, with limited fruitful intervention to control the manifestations of DFUs. Resveratrol (RV) can improve endothelial function and has strong pro-angiogenic properties for the treatment of diabetic foot wounds. The present study aims to design an RV-loaded liposome-in-hydrogel system to effectively heal diabetic foot ulcers. A thin-film hydration method was used to prepare RV-loaded liposomes. Liposomal vesicles were assessed, for various characteristics such as particle size, zeta potential, and entrapment efficiency. The best-prepared liposomal vesicle was then incorporated into 1% carbopol 940 gel to develop a hydrogel system. The RV-loaded liposomal gel showed improved skin penetration. To assess the efficacy of the developed formulation, a diabetic foot ulcer animal model was used. The topical application of the developed formulation significantly reduced blood glucose and increased glycosaminoglycans (GAGs) to improve ulcer healing as well as wound closure on day 9. Faster re-epithelization, proliferation of fibroblast, formation of collagen, and reduced inflammatory cell infiltration at the wound site were also noted. Results indicate that RV-loaded liposomes in hydrogel-based wound dressing significantly accelerate wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetics.

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