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.
Schematic overview of the biotin-loaded acacia–alginate nanogel (BOT–ACC–SA) and its in vivo wound-healing performance. The formulation strategy (biotin incorporated within an acacia gum–coated alginate nanogel) is linked to accelerated macroscopic wound closure (Day 0–14) across treatment groups, with BOT–ACC–SA producing the highest closure. The enhanced healing response is associated with early granulation and reduced inflammation, alongside upregulation of tissue-regeneration biomarkers (VEGF, TGF-β1, and Collagen I).