Nanogel therapy for chronic and post-surgical wounds: a bioengineered Lactoferrin-Acacia-Alginate system enhancing tissue regeneration and inflammatory resolution.

Chronic and post-surgical wounds often exhibit poor angiogenesis, persistent inflammation, and delayed tissue remodeling. Lactoferrin (LAC), a multifunctional glycoprotein with immunomodulatory and healing properties, faces challenges like low solubility and enzymatic degradation that limit its therapeutic use. This study developed a topical nanogel system incorporating LAC, acacia gum (ACC), and sodium alginate (SA) to improve stability, local delivery, and wound healing efficacy. A LAC-ACC complex was formed through adsorption and embedded into SA-based nanogels (Formulations A-C), with Formulation B (2.5 % SA) optimized based on physicochemical and rheological properties. Characterisation techniques included particle size analysis (DLS), thermal profiling (DSC), molecular interaction (FT-IR), crystallinity evaluation (XRD), morphological analysis (TEM), and viscoelastic property determination (rheology). The optimized nanogel exhibited nanoscale size (120.2  nm), low PDI (0.18), and improved solubility (∼2.9-fold). It sustained LAC release up to 82.5 % over 24  h and remained stable for 12 months. In vivo, the LAC-ACC-SA nanogel achieved 95.3 % wound closure by day 14 in rats, significantly outperforming LAC-SA gel, blank gel, and untreated control. The nanogel formulation enhanced VEGF, TGF-β1, and Collagen I expression while reducing IL-6 levels, collectively supporting accelerated tissue regeneration. This nanogel system demonstrates strong potential for managing chronic and post-operative wounds through improved protein delivery and modulation of wound healing pathways.