Development and Characterization of a Novel Hydrogel Dressing for Co-delivery of Resveratrol and Gallic acid via Cyclodextrin Inclusion Complexation for Wound Healing

Abstract

Background: The therapeutic potential of polyphenols like resveratrol (Res) and gallic acid (GA) in wound healing is limited by their poor aqueous solubility and chemical instability. This study aimed to develop and characterize a novel hydrogel-based drug delivery system to overcome these limitations and achieve synergistic therapeutic effects. Methods: The strategy involved two key components, a Res/GA inclusion complex (Res/GA-IC) prepared using hydroxypropyl-β-cyclodextrin (HP-β-CD) to enhance polyphenol solubility and stability, and a dual-crosslinked carboxymethyl cellulose-poly(vinyl alcohol) (CMC-PVA) hydrogel formulated as a delivery vehicle for the IC. The properties of the Res/GA-IC and the final hydrogel patch were characterized. Results: Formulation of the Res/GA-IC resulted in a remarkable increase in the aqueous solubility of Res. The Res/GA combination showed strong synergistic antioxidant activity (CI < 0.3), and the Res/GA-IC demonstrated enhanced antibacterial efficacy against Staphylococcus aureus. The CMC-PVA hydrogel dressing incorporating the IC showed favorable physicochemical properties, including appropriate swelling capacity, structural integrity, and sustained release characteristics for both active agents. Crucially, the final formulation was highly biocompatible with human fibroblast cells. Conclusion: This work presented a successful formulation strategy for the co-delivery of poorly soluble synergistic polyphenols. The developed hydrogel dressing represents a promising therapeutic platform for advanced wound management by effectively addressing key challenges of oxidative stress and bacterial infection.

Keywords: Resveratrol, gallic acid, inclusion complex, hydrogel, wound healing