Hydrophobic deep eutectic solvent-based microemulsions for enhanced anti-inflammatory effect

Curcuminoids (CUN), found in Curcuma longa, are the key bioactive components responsible for antioxidant and anti-inflammatory effects. This study developed and evaluated the CUN microemulsions (ME) formulated with hydrophobic deep eutectic solvents (HDES) of menthol and oleic acid as oil phase (HDES-based ME). The ternary ME system consisted of oil, surfactant and water, with increasing water content (10–40%), reduced droplet size (< 120 nm) and improved monodispersity. Most MEs suppressed nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, whereas ME8, ME13 and ME15 appeared immunologically neutral. CUN in HDES-based ME markedly inhibited nitric oxide (NO) generation, achieving nearly 80% suppression. Oxidative stress analysis revealed that LPS markedly elevated intracellular reactive oxygen species (ROS) levels compared with L-NAME controls. CUN in both carriers reduced ROS generation in a dose-dependent manner (0.195–12.5 µg/mL), with HDES-based ME consistently outperforming DMSO. These findings demonstrate that HDES-based ME is a biocompatible carrier capable of enhancing the anti-inflammatory efficacy of CUN.