Synergistic nanogel therapy for dry and nutrient-deficient wounds: biotin-loaded acacia-alginate hydrogel enhances tissue regeneration and reduces inflammation.

Dry, nutrient-poor wounds often heal slowly because inflammation persists and tissue repair is impaired. This study developed a biotin-loaded acacia-alginate nanogel (BOT-ACC-SA) to improve biotin's poor water solubility, limited skin penetration, and therapeutic performance in wound healing. Biotin was first adsorbed onto acacia gum and then incorporated into sodium alginate nanogels using sonication-assisted self-assembly. The formulation was thoroughly characterized by thermal, spectroscopic, crystallographic, microscopic, particle-size, and rheological analyses. The optimized nanogel showed a mean size of about 120 nm, a zeta potential of -32.7 mV, and high encapsulation efficiency (90.1%). It increased biotin solubility 2.8-fold and released 97% of the drug within 24 hours, following the Higuchi release model. In vivo evaluation in Wistar rats over 14 days demonstrated superior wound closure with BOT-ACC-SA (94.6%) compared with BOT-SA, ACC-SA, and untreated controls. The nanogel also significantly increased VEGF, TGF-β1, and collagen I while reducing IL-6, indicating enhanced angiogenesis, extracellular matrix remodeling, and inflammation resolution. Stability testing confirmed that the formulation remained stable for 12 months at refrigerated conditions. Overall, BOT-ACC-SA appears to be a promising topical treatment for difficult-to-heal wounds.