Menthol–Fatty Acid HDES Boosts In Vitro Oral Bioavailability of Oleanolic Acid via Synergistic Digestive Release and Cellular Absorption

Imagine a natural compound with powerful health benefits that your body barely absorbs—oleanolic acid's bioavailability just got a 9.3-fold boost, thanks to a clever solvent trick.

Oleanolic acid (OA) is a bioactive compound with promising therapeutic potential, but its poor oral bioavailability has long been a bottleneck. Now, researchers have engineered a solution using a hydrophobic deep eutectic solvent (HDES) made from menthol and fatty acids. In simulated digestion and Caco-2 cell transport models, this HDES dramatically improved OA's apparent bioavailability index by 9.3-fold compared to conventional ethanol systems—and the effect depended on the fatty acid chain length.

The mechanism unfolds in two stages. During digestion, HDES boosted OA bioaccessibility to 14.30%, versus 4.90% with ethanol. Then, during absorption, cellular uptake jumped to 25.79%, compared to just 4.71% with ethanol. Spectral analysis and cellular studies revealed that HDES's optimal hydrophobicity and diffusion properties drive this synergistic enhancement.

This work uncovers a chain-length-dependent mechanism in HDES-facilitated delivery, offering a tunable strategy to improve the absorption of hydrophobic bioactive compounds. It's a step toward unlocking the full potential of natural products—without the need for complex chemical modifications.

Key Points

• HDES boosts OA bioavailability 9.3-fold vs ethanol
• Two-stage enhancement: digestion and absorption
• Fatty acid chain length tunes efficacy