A novel peppermint essential oil nanoemulsion based on co-assembly of hydrophilic and hydrophobic deep eutectic solvents: Preparation, characterization and biological activity

Deep eutectic solvents (DESs) have shown great potential in the sustainable fabrication of nanoemulsions. However, co-assembled nanoemulsion systems that integrate both hydrophilic DES (HL-DES) and hydrophobic DES (HB-DES) (referred to as HL/HB-DES-NE) have yet to be reported. In this study, we designed and fabricated a novel HL/HB-DES-NE system and utilized it for encapsulating peppermint essential oil (PMEO). The formulation was systematically optimized, and the resulting HL/HB-DES-NE was characterized for particle size, particle size distribution, encapsulation efficiency, stability, anti-inflammatory activity and antibacterial activity. Firstly, a hydrophobic DES was prepared through eutectic mixing of thymol and polyglyceryl-4-caprate, while a hydrophilic DES was synthesized using betaine and glycerol. The optimal formulation is PMEO/thymol:polyglyceryl-4-caprate (2:1, mol/mol)/betaine:glycerol (1:3, mol/mol)/H₂O [0.275/0.25/0.94/3.76, v/v/v/v] which achieved a particle size of approximately 55.80 nm. The nanoemulsions exhibited good anti-inflammatory and antibacterial activities and maintained remarkable stability, showing no significant changes in particle size, distribution, anti-inflammatory activity and antibacterial activity after 14 days of storage at 4 °C, 20 °C, 37 °C, and 55 °C. The proposed co-assembly strategy, which leverages the unique properties of both hydrophilic and hydrophobic DESs, offers a green alternative to traditional surfactants and provides a flexible and scalable platform for the design of high-performance nanoemulsions. The findings not only provide important theoretical and practical foundations for the development of essential oil-based antimicrobial and anti-inflammatory agents in cosmetics, pharmaceuticals, and industrial applications, but also propose a novel strategy for the development of next-generation DES-based formulations across diverse industries.