Interfacial chemistry modulates lipophilic nutraceuticals supersaturation and digestion profile in food-grade microemulsions.

Supersaturation improves the apparent solubility of lipophilic nutraceuticals but is constrained by crystallization and limited stability. This study elucidates how interfacial molecular organization in microemulsions governs curcumin supersaturation stabilization. An optimal supersaturation degree (50-200-fold) was identified, within which over 80% of the initial supersaturation was preserved during storage and upon gastrointestinal dilution, whereas excessive loading (300-fold) triggered crystallization and loss of metastability. 1H NMR analysis revealed progressive upfield shifts of Tween 80 α1-CH2/α2-CH2 protons, accompanied by perturbations in curcumin aromatic and olefinic signals, indicating preferential localization within the spatially confined interfacial layer. This interfacial partitioning likely restricts molecular mobility and suppresses nucleation. Functionally, microemulsions enhanced intestinal transport and bioavailability of curcumin. Bioavailability increased within the 50-200-fold range but declined at higher supersaturation due to aggregation during digestion. This work establishes a structure-function relationship between interfacial organization and supersaturation stability, providing a rational basis for designing high-performance delivery systems for lipophilic bioactives.