Pharmacological evaluation of a Brucine-loaded nanoemulgel for enhanced wound healing through in-silico and in-vivo investigations

Wound healing is a vital biological process that restores damaged tissue. In diabetes, this process slows down due to chronic inflammation and oxidative stress. Brucine, a natural compound from Nux vomica, is known for its anti-inflammatory and antioxidant actions and its ability to promote fibroblast growth. However, its poor solubility and toxicity limit its clinical use. To address these issues, a nanoemulgel formulation was developed to improve the delivery and wound-healing effectiveness of brucine. The study aimed to develop and evaluate a brucine-loaded nanoemulgel for wound healing. The objectives were to (i) study molecular interactions of brucine with wound-healing proteins using in-silico analysis, (ii) prepare and characterize the nanoemulgel, and (iii) test its wound-healing ability in diabetic rats. Molecular docking was performed using AutoDock 4.1 to predict brucine's binding with proteins involved in fibroblast proliferation and tissue repair. The nanoemulgel was prepared by incorporating brucine-loaded nanoemulsion into a hydrogel base. Its drug release, skin permeation, and stability were tested using standard laboratory techniques. Wound healing was evaluated in streptozotocin-induced diabetic rats by measuring wound closure over 14 days and analyzing tissue samples microscopically. Docking results showed strong binding of brucine with fibroblast growth factor receptor (FGFR, - 9.63 kcal/mol) and epidermal growth factor receptor (EGFR, - 9.17 kcal/mol), indicating its potential to stimulate cell growth and repair. The nanoemulgel showed 1.8-fold higher drug permeation and controlled release up to 12 h compared to plain gel. In diabetic rats, wounds treated with brucine nanoemulgel showed 80% closure by day 14, compared to 65% with standard treatment and 40% in untreated controls. Histopathology confirmed better collagen formation, fibroblast proliferation, and reduced inflammation. The brucine-loaded nanoemulgel improved drug delivery and significantly accelerated diabetic wound healing. It enhanced fibroblast activity and tissue repair while minimizing inflammation. This nanoformulation offers a promising topical strategy for chronic wound management, warranting further stability and clinical studies.