Abstract

The water insolubility of curcumin and turmeric oils limits their extraction, stability, and bioavailability. In this study, hydrophobic deep eutectic solvent (HDES)-based microemulsion (ME) and its water-free form was used to enhance the solubility, stability and efficacy of curcuminoids. HDESs using menthol paired with short-chain fatty acids notably increased curcuminoid solubility compared to those with medium-chain fatty acids. The oil phase of the ME, a lactic acid:menthol (2:1 mass ratio) mixture, along with a surfactant mixture of Tween 80:propylene glycol (1:1 mass ratio) and choline chloride:propylene glycol (1:3 M ratio) at a ratio of 4:5:1, significantly improved the water solubility of the target compounds. Solubility of bisdemethoxycurcumin, demethoxycurcumin, curcumin, and aromatic-turmerone reached 30.2 ± 0.1, 15.6 ± 0.0, 20.5 ± 0.0, and 49.3 ± 0.1 mg/mL, respectively, with stability at 60 °C. The lactic acid and menthol (HDES)-ME outperformed the acetic acid and menthol variants in terms of target compound stability. Curcuma longa L. extract in MEs exhibited anti-inflammatory activity in lipopolysaccharide-induced RAW264.7 cells, with an IC<inf>50</inf> of 0.448–1.55 μg/mL for curcumin, surpassing its effect in DMSO (IC<inf>50</inf> = 3.57 μg/mL). These DES-based MEs offer the dual benefits of increased solubility and anti-inflammatory effects, suggesting their potential for use in improving the bioavailability of bioactive compounds.