Design and Characterization of Azithromycin-Loaded Pectin-Hyaluronic Acid Nano Hydrogel for the Treatment of Skin Infections

Purpose: Skin infections remain a major clinical concern due to rising antimicrobial resistance and the poor skin penetration of conventional topical formulations. This study developed and characterised an azithromycin -loaded novasome-incorporated pectin­hyaluronic acid nano hydrogel formulation for localised drug delivery in skin infections, designed to enhance skin retention, penetration, and controlled drug release.
Methods: Azithromycin-loaded novasomes (stearic acid, oleic acid, Span 80, cholesterol) were prepared by ethanol injection and optimised via a design-of-experiments for minimum particle size and maximum drug loading. Optimised novasomes were incorporated into a pectin­ hyaluronic acid-gellan gum hydrogel, cross-linked with tartaric acid, and evaluated for physicochemical properties, FTIR compatibility, sterility, in-vitro drug release, ex-vivo skin permeation, antibacterial efficacy, and in vivo wound healing in a S. aureus-infected rodent model with histopathological analysis.
Results: Optimised novasomes showed a particle size of 118.7±39.7 nm and drug loading of 66.762±0.013%. The nano hydrogel exhibited skin-compatible pH (5.286±0.015), spreadability (75±0.577 g.cm/s), and viscosity (37,500±358.573 cP) with shear-thinning behaviour. FTIR confirmed no drug-excipient interaction. The nanogel showed sustained, controlled drug release and greater ex-vivo skin permeation than the marketed gel, with larger zones of inhibition against S. aureus. In-vivo, the nanogel produced faster wound contraction and near-complete healing by Day 15, with histopathology confirming enhanced re­epithelialization, collagen deposition and fibroblast proliferation.
Conclusion: The novasome-loaded nano hydrogel offers a promising controlled-release topical platform for effective azithromycin delivery in bacterial skin infections.