Sustainable production of nanoemulsions by membrane-assisted nanoemulsification using novel aroma-based hydrophobic deep eutectic solvents for enhanced antifungal activities

Hydrophobic deep eutectic solvents (DESs), a recent class of green solvents, offer 100% atom economy, low cost, potential biodegradability, negligible toxicity and promising bioactivities. In this work, novel aroma-based therapeutic hydrophobic DESs were prepared and dispersed in aqueous media as nanoemulsions to potentiate biomedical applications, where polar media is encountered. A reusable microengineered stainless-steel isoporous membrane was fabricated by laser drilling technique. Three hydrophobic DESs, namely DES A (menthol and vanillin), DES B (menthol and raspberry ketone), and DES C (thymol and raspberry ketone) were prepared and emulsified in aqueous media by sustainable membrane emulsification technique. The optimised nanoemulsion (DES C-in-water) exhibited a monomodal size distribution with Zavg (size average) of 147 nm and polydispersity index of 0.22. From the application perspective, the formulated DES-in-water nanoemulsions and their constituents were evaluated for their antibacterial properties against Escherichia coli and Staphylococcus aureus. Additionally, antifungal properties of the DES-based emulsions were reported for the first time by testing them against four fungal strains, Aspergillus fumigatus, Candida albicans, Candida krusei, and Trichophyton mentagrophytes. The nanoemulsions were found to be exhibit antimicrobial effect and lesser quantities of individual compounds were needed in nanoemulsified state to show similar effects. Different 1D and 2D NMR techniques were successfully used to investigate the structural orientation and the inter and intramolecular interactions in the DES and emulsion systems, which revealed a probable cause for higher antimicrobial activity of DES C-based emulsions compared to its peers. Lastly, a synergistic effect of the components in nanoemulsions led to enhanced antimicrobial activities.