Eugenol microemulsions exhibit potent activity against drug-resistant diabetic foot ulcer pathogens: Toward...

Diabetic foot ulcers (DFUs) are chronic, non-healing wounds that are often infected with multidrug-resistant pathogens, such as Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Biofilm formation and oxidative stress further aggravate the treatment. This study focuses on the preparation and evaluation of a stable eugenol microemulsion (EuME) as a potential nanotherapeutic candidate for DFU-associated infections. EuME was formulated using a pseudo-ternary phase diagram approach to optimize surfactant concentration in an oil-in-water system. Deionized water was gradually added to the oil-surfactant mixture under magnetic stirring, and formulations were selected based on low surfactant concentration, reduced toxicity, and good kinetic stability. Nanodroplet formation (∼13 nm) and structural stability were confirmed using DLS, FTIR, and TEM. Antimicrobial efficacy was evaluated using zone-of-inhibition, MIC, and MBEC assays. FE-SEM revealed strong antibiofilm activity, bacterial cell disintegration, and membrane damage in multidrug-resistant clinical isolates. Biochemical assays demonstrated significantly reduced ROS generation (P < 0.001), with 94-98% inhibition of catalase and SOD activities, and decreased lipid peroxidation. Collectively, these findings highlight the potent antibacterial and antioxidant properties of EuME, supporting its potential as a nanocomposite-based wound-healing agent for DFUs and warranting further preclinical evaluation.