Pickering high internal phase emulsions stabilized by soy protein isolate/κ-carrageenan complex for enhanced stability, bioavailability, and absorption mechanisms of nobiletin.

Nobiletin (NOB), a lipid-soluble polymethoxyflavone with potent antioxidant, antimicrobial, and anti-inflammatory properties, suffers from poor stability and pH sensitivity, limiting its bioavailability. In this study, Pickering high internal phase emulsions (HIPEs) stabilized by soy protein isolate (SPI) and κ-carrageenan (KC) were developed to encapsulate and protect NOB. The emulsions, containing a 75 % medium-chain triglyceride (MCT) volume fraction, were optimized by investigating the effects of pH and KC concentration on the key properties such as the creaming index, particle size, zeta potential, microstructure, and rheology. Results showed that under optimal conditions (pH 7 and 1.0 % KC), the SPI/KC HIPEs exhibited improved physicochemical properties. Furthermore, encapsulation of NOB in HIPEs significantly improved its stability against UV exposure, heat, and storage conditions. Additionally, simulated gastrointestinal digestion studies revealed that the SPI/KC HIPEs improved the digestion stability and bioaccessibility of NOB, with controlled release in the intestinal phase. Moreover, the SPI/KC HIPEs facilitated increased cellular uptake and bioavailability of NOB, with clathrin-mediated endocytosis and macropinocytosis as primary absorption pathways. The encapsulated NOB also showed enhanced inhibition of inflammatory markers, including NO, IL-6, and TNF-α. These findings suggested that SPI/KC HIPEs provided a promising delivery system for improving the bioavailability and bioactivity of hydrophobic compounds.