On the role of components of therapeutic hydrophobic deep eutectic solvent-based nanoemulsions sustainably produced by membrane-assisted nanoemulsification for enhanced antimicrobial activity

Stringent regulations and growing industrial interests have ensued the development of sustainable processes. Membrane assisted-nanoemulsification based on microengineered membranes has been explored for the sustainable production of therapeutic hydrophobic deep eutectic solvent (DES)-based nanoemulsions for enhanced antimicrobial applications. Hydrophobic DESs were synthesised by employing therapeutic terpenes: DL-menthol and thymol. To understand the mechanism of oil droplet detachment from the membrane when producing such nanoemulsions, the effect of hydrophilicity/hydrophobicity partition of the active membrane surface on the process performance was evaluated. Using a continuous phase cross-flow velocity of 0.32 m.s⁻¹, a dispersed phase flowrate of 0.02 ml.min⁻¹ and 2% (w/w) Tween 80 resulted in a DES-in-water nanoemulsion of 81.2 ± 0.9 nm droplet size. Novel observations like intrinsically reduced interfacial tension of 7.5 mN.m⁻¹ between water and hydrophobic DES, and a hydrophobic DES wetting behaviour to both hydrophilic and hydrophobic active membrane surfaces were witnessed. Compared to DL-menthol, thymol or synthesised DES, the optimised DES-in-water nanoemulsions exhibited enhanced synergetic antimicrobial effect against Escherichia coli, Staphylococcus aureus and superior potency against Cutibacterium acnes, an acne inducing bacterial strain. These nanoemulsions were also cytocompatible with human keratinocytes and dermal fibroblasts. Lastly, membrane-assisted nanoemulsification manifested controlled size and monomodally distributed nanoemulsions compared to traditional ultrasound-driven emulsification.