Epigallocatechin Gallate (EGCG)-Loaded Hydrogel for Topical Chronic Non-Communicable Skin Inflammation

Abstract Purpose Chronic non-communicable inflammatory skin disorders involve persistent immune activation, oxidative stress, and impaired repair. Conventional topical agents such as corticosteroids often cause adverse effects with long-term use. Epigallocatechin-3-gallate (EGCG), a potent antioxidant and anti-inflammatory polyphenol, shows therapeutic potential but is limited by poor stability and permeability. Hydroxypropyl methylcellulose-based hydrogels (HPMC-gel) offer a biocompatible platform for topical drug delivery with sustained release. Methods EGCG-loaded HPMC gels were formulated with or without 10% propylene glycol (PG). Differential Scanning Calorimetry assessed thermal stability. Release behaviours were measured in a permeable insert system using High-Performance Liquid Chromatography with Ultraviolet Detection (HPLC-UV). Cytocompatibility was tested via XTT assay on EA.hy926 endothelial cells and human dermal fibroblasts. Cellular uptake, cytokine modulation, and ROS levels were quantified following tumour necrosis factor-alpha (TNF-α) stimulation to simulate inflammatory conditions. Results EGCG exhibited cytocompatibility up to 0.5 µM in both cell types. Differential Scanning Calorimetry (DSC) revealed a higher glass transition temperature in EGCG-HPMC gels compared to plain HPMC. The gel formulations provided sustained EGCG release over six hours, with PG-containing gels showing moderately increased permeation. Cellular uptake studies demonstrated significantly higher intracellular EGCG levels from gel + PG formulations compared to solution or gel alone ( p < 0.0001). Under TNF-α stimulation, EGCG markedly reduced Interleukin-6 (IL-6) and Interleukin-8 (IL-8) secretion, suppressed MMP-9, and modulated TGF-β1 expression. EGCG treatment also attenuated intracellular ROS accumulation in a dose-dependent manner. Conclusion The EGCG-HPMC gel demonstrated favourable biocompatibility, enhanced stability, sustained release, and robust anti-inflammatory, antioxidant, and matrix-modulating effects in vitro. This biocompatible formulation offers a promising topical therapy for chronic inflammatory skin disorders.