Box–Behnken design optimization of Allium cepa (onion) peels extract-loaded chitosan nanoparticles for enhanced antibacterial and antioxidant activity with in-silico mechanistic insights

Agricultural and food waste poses environmental challenges while providing a valuable source of bioactive compounds. This study valorised Allium cepa (red onion) peel waste by developing and optimizing chitosan nanoparticles encapsulating phenolic-rich onion peel extract (CS/OE-NPs), based on the hypothesis that nanoencapsulation would enhance extract stability and antibacterial efficacy while preserving antioxidant activity. A Box–Behnken design was employed for formulation optimization, and molecular docking was performed to investigate the interactions of the major GC-MS-identified furanone constituent with bacterial protein targets. The optimized formulation was comprehensively characterized, confirming successful nanoparticles (NPs) formation and efficient extract encapsulation. CS/OE-NPs exhibited superior antioxidant activity (89.58%) with the lowest IC₅₀ (0.49 mg/mL), compared with free OE (85.04%, IC₅₀ = 0.54 mg/mL). Notably, although CS/OE-NPs contained only ~ 26% loaded OE (~ 0.127 mg/mL within 0.49 mg/mL NPs), they retained antioxidant activity comparable to the free extract, demonstrating that nanoencapsulation effectively preserved the bioactivity of the encapsulated phytochemicals. Release studies revealed pH-responsive sustained release governed by diffusion and matrix erosion. Furthermore, CS/OE-NPs showed markedly enhanced antibacterial activity (IC₅₀: 0.001 mg/mL against E. coli and 0.00285 mg/mL against S. aureus ) compared with free OE. Molecular docking supported these findings by demonstrating strong binding affinities between onion peel phytochemicals and bacterial protein targets. Overall, CS/OE-NPs represent a promising natural nanoformulation for antioxidant and antibacterial applications, promoting the sustainable valorisation of agri-food waste for biomedical and environmental applications.