Topical treatment of diabetic foot ulcers using a novel quercetin-loaded hyaluosome gel nanoformulation
Abstract
Diabetic foot ulcers (DFUs) are among the most severe and debilitating complications of diabetes mellitus, often progressing to limb amputation due to persistent, non-healing lesions. Because of the multifactorial pathogenesis of DFUs, there is a pressing demand for novel drug delivery approaches capable of enhancing treatment effectiveness. This study aimed to enhance topical drug delivery for DFU management through the formulation and optimization of a Quercetin-loaded hyaluosome gel (QCN-HS). The nanoformulation was prepared and characterized, followed by in vitro and in vivo evaluations. The optimized QCN-HS demonstrated an entrapment efficiency of 88.1%, a mean particle size of 122.42 nm, and a zeta potential of − 24 mV. Morphological assessment by transmission electron microscopy revealed a uniform cuboidal-to-rounded square architecture without aggregation, further validated by FTIR spectroscopy. QCN-HS significantly reduced the expression of pro-inflammatory cytokines (TGF-β, TNF-α, IL-17, and IL-6) and lowered MPO activity, while markedly increasing GST and GSH levels. Moreover, QCN-HS downregulated ADAMTS-5 and MMP-13 while upregulating TIMP-3, findings corroborated by scratch assay and IC50 data, confirming effective regulation of extracellular matrix turnover. Histological and immunohistochemical analyses further demonstrated significant suppression of NF-κB expression in skin tissue. The quercetin-loaded hyaluosome gel, with favorable physicochemical properties…
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