An Innovative Dual-Drug Topical Hydrogel for Synergistic Wound Healing: Formulation and Evaluation

Abstract

Purpose

This study aimed to develop and evaluate a dual-drug topical hydrogel incorporating doxycycline and voriconazole to enhance wound healing by addressing polymicrobial infections commonly associated with chronic wounds.

Methods

The hydrogel was formulated using Poloxamer 407 and sodium alginate as gelling agents, incorporating optimized concentrations of both drugs. Preformulation studies (FTIR, DSC) confirmed drug-excipient compatibility. Physicochemical evaluations included pH (measured directly), spreadability, viscosity, and appearance. Rheological properties were assessed across varying shear rates. In vitro drug release was evaluated using Franz diffusion cells, and release kinetics were modeled using Korsmeyer–Peppas, Higuchi, and first-order models. Antibacterial and antifungal activities were tested against Escherichia coli, Bacillus subtilis, and Rhizopus arrhizus, selected for their clinical relevance. An excision wound model in Wistar rats assessed in vivo healing, supported by histopathology. Stability studies were conducted under accelerated conditions (40 ± 2 °C, 75% RH, 30 days).

Results

The optimized hydrogel showed ideal pH (6.5 ± 0.2), high spreadability (22.1 ± 1.5 g·cm/sec), and appropriate viscosity (4,100 ± 120 cP). Drug release was sustained over 24 h (doxycycline: 86.2 ± 3.1%; voriconazole: 79.5 ± 2.8%), fitting the Korsmeyer–Peppas model (R² >0.97). The hydrogel exhibited strong antimicrobial activity and achieved 96.5% wound contraction by Day 16, significantly outperforming controls and single-drug treatments (p < 0.01). Histological analysis confirmed improved granulation and collagen deposition.

Conclusion

The dual-drug hydrogel offers a synergistic, biocompatible, and stable platform for managing chronic polymicrobial wounds, demonstrating promising therapeutic potential.