Mechanistic insights and functional evaluation of an Artemisia annua essential oil nanoemulsion for antibacterial topical application against Staphylococcus aureus

In this study, an Artemisia annua essential oil nanoemulsion (AEON) was prepared via ultrasonic emulsification and systematically characterized, exhibiting a mean particle size of 9.02 ± 0.54 nm, a polydispersity index (PDI) of 0.236 ± 0.020, and a zeta potential of -40.23 ± 3.19 mV, indicative of excellent colloidal stability for biomedical use. AEON showed potent antibacterial activity against Staphylococcus aureus (S. aureus) with a minimum inhibitory concentration (MIC) of 5 μL/mL. Untargeted metabolomics revealed disruptions in glycerophospholipid metabolism, fatty acid biosynthesis, and purine metabolism, correlating with increased membrane fluidity and potential, enhanced permeability, reduced hydrophobicity, impaired peptidoglycan integrity, and elevated intracellular ROS levels, indicating combined membrane destabilization and oxidative stress. To assess practical applicability in preventing pathogen transmission, AEON was formulated into a composite topical formulation (ACTF), which displayed excellent physical stability under storage and stress conditions, maintained robust antibacterial efficacy in vitro, and effectively reduced bacterial infection in a rat skin model. Safety assessments showed no dermal toxicity, and sensory testing confirmed good user acceptability. Overall, AEON-based formulations show strong potential as natural antimicrobial agents for integration into topical products aimed at preventing or managing skin infections caused by S. aureus.