Natural Deep Eutectic Solvents Enhance the Bioavailability and Antioxidant Activity of Oleanolic Acid in Self-Constructed Pickering High Internal Phase Emulsions

Oleanolic acid (OA)-stabilized water-in-oil Pickering high internal phase emulsions (HIPEs), using natural deep eutectic solvents (NADESs) as the internal phase (HIPE-NADES), were developed to enhance OA bioavailability. Three kinds of NADESs (proline: sorbitol (1:1), proline: glucose (1:1), and proline: glucose (5:3)) were selected, and HIPEs with pure water as the internal phase were used as the control group. In vitro digestion and Caco-2 models showed that HIPE-NADES significantly improved OA bioaccessibility via enhanced stability and solubility. Crucially, OA bioavailability reached 16.20–19.10%, markedly surpassing controls (p ≤ 0.05), indicating that NADESs’ hydrogen-bonding network facilitates intestinal uptake. In a t-BHP-induced Caco-2 oxidative stress model, OA-loaded HIPE-NADES significantly attenuated damage, reducing MDA and ROS while elevating GSH-Px, CAT, and SOD activities and GSH levels (p ≤ 0.05). NADESs themselves contributed substantially to antioxidant efficacy. HIPE-NADESs represent an effective platform for enhancing the bioavailability and bioactivity of hydrophobic phytochemicals like OA, enabling simpler and more stable delivery systems.