Piceatannol-loaded self-nanoemulsifying drug delivery system accelerates wound healing in diabetic rats

Objective: To evaluate the effects of a piceatannol-loaded self-nanoemulsifying drug delivery system (PIC-SNEDDS) on wound healing in diabetic rats and its mechanisms of wound healing action. Methods: Diabetes was induced in rats using streptozotocin, after which full-thickness excisional wounds were created. Piceatannol was administered topically either as a raw hydrogel or formulated into a PIC-SNEDDS, which was prepared using an optimized oil-surfactant mixture and incorporated into a hydrogel for application. Wound healing activity was assessed through measurements of wound contraction, oxidative stress biomarkers, and collagen content, along with histological and immunohistochemical evaluation of inflammatory, angiogenic, and remodeling markers. Results: PIC-SNEDDS markedly enhanced diabetic wound healing by promoting epithelial regeneration, granulation tissue formation, epidermal proliferation, and keratinization. The formulation also reduced the expression of pro-inflammatory markers (interleukin-6, nuclear factor-kappa B, and tumor necrosis factor-α) while increasing α-smooth muscle actin, transforming growth factor-β1, vascular endothelial growth factor-A, and hydroxyproline levels. Additionally, it improved antioxidant status by lowering malondialdehyde levels and boosting superoxide dismutase and catalase activity, along with upregulation of COL1A1 mRNA expression. Conclusions: PIC-SNEDDS promotes the healing of diabetic wounds and exhibits anti-inflammatory, antioxidant, pro-collagen, and angiogenic properties.