Paeonol Nanoemulgel as a Novel Topical Approach for Accelerated Healing of Diabetic Wounds in Rats

Diabetic wounds are characterized by persistent inflammation, oxidative stress, impaired angiogenesis, and delayed tissue regeneration. This study developed and evaluated a paeonol-loaded nanoemulgel for improving diabetic wound healing. The nanoemulsion was prepared using cinnamon oil, Cremophor RH 40, and Transcutol P and incorporated into a Carbopol 940 gel. The optimized formulation was characterized for particle size, polydispersity index, zeta potential, drug content, entrapment efficiency, pH, viscosity, in vitro drug release, ex vivo skin permeation, and stability. Its therapeutic efficacy was investigated in a streptozotocin–nicotinamide-induced diabetic excisional wound model in male Wistar rats. Animals were assigned to negative-control, vehicle-control, silver-sulfadiazine, paeonol-loaded nanoemulgel, and plain-paeonol groups. The optimized nanoemulgel exhibited satisfactory physicochemical stability, sustained drug release, enhanced skin permeation, and no clinically significant dermal irritation. Treatment with the paeonol-loaded nanoemulgel produced significantly greater wound contraction and a shorter epithelialization period than the negative-control, vehicle-control, and plain-paeonol treatments (p < 0.05). Histopathological examination demonstrated reduced inflammatory-cell infiltration, enhanced re-epithelialization, increased granulation-tissue formation, improved angiogenesis, and greater collagen deposition. Biochemical analysis revealed significant reductions in oxidative stress and the pro-inflammatory cytokines TNF-α and IL-1β, together with increased vascular endothelial growth factor expression (p < 0.05). These findings indicate that nanoemulgel-based topical delivery enhances the wound-healing activity of paeonol and represents a promising strategy for managing diabetic wounds.