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

Abstract

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.

Keywords

Angiogenic activities / Diabetic wound healing / Piceatannol / Self-nanoemulsifying drug delivery system

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

This project was funded by the Deanship of Scientific Research at King Abdulaziz University, Jeddah, under Grant No. G: 534-1401443.

Data availability statement

The data supporting the findings of this study are available from the corresponding author upon request.

Authors’ contributions

MHJ, RSA, and BGE formulated the research concept and designed the study. RSA and ABA carried out the data collection and methodological procedures. RSA, MHJ, and DMB performed the data analysis. MHJ, DA and RM performed the data interpretation. ABA conducted validation of the experimental findings. DA, and RM contributed to data visualization. MHJ, BGE and DMB supervised the project. MHJ obtained the project funding. RSA and MHJ prepared the original manuscript draft, and BGE, DMB, ABA, DA, and RM critically revised the manuscript for important intellectual content. All authors reviewed and approved the final version of the manuscript for publication.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Acknowledgments

The authors acknowledge the Deanship of Scientific Research at King Abdulaziz University, Jeddah, Saudi Arabia, for technical and financial support. We thank Dr. Rasheed Ahemad Shark for his assistance with animal laboratory experiments. The completion of this work by Rawan S AlRashdi partially fulfilled the requirements for the Master’s Degree program in Clinical Pharmacology.

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