Food-grade Pickering emulsions for dual-targeted delivery of dietary bioactives to the colon and inflamed sites: A synergistic strategy for alleviating ulcerative colitis

Dietary bioactives and their combinations hold considerable promise for alleviating ulcerative colitis (UC). However, their use is often constrained by poor solubility, low bioavailability, and rapid clearance. To address these limitations, we developed a dual-targeted, food-grade Pickering emulsion engineered to respond to the gastrointestinal environment for improved dietary intervention in UC. Specifically, fish oil Pickering emulsions were stabilized with curcumin (Cur)–loaded shellac nanoparticles (CLSNPs) in combination with chitosan (CS). CLSNPs effectively encapsulated Cur and stabilized the oil–water interface through interactions with CS. The resulting Pickering emulsion remained highly stable in simulated gastric fluid but transformed into an emulsion gel in simulated small intestinal fluid via CS gelling. This transition prevented premature digestion and ensured safe delivery to the colon. In the colon, gut microbiota degraded the gelled emulsion, enabling the controlled release of fish oil and CLSNPs. The intrinsic negative charge of CLSNPs promoted selective binding to positively charged inflammatory sites, enhancing the therapeutic action of Cur, while fish oil contributed to restoring gut microbiota balance. In a dextran sulfate sodium–induced UC mouse model, this emulsion system significantly improved intestinal barrier repair, immune modulation, and gut microbiota regulation. Collectively, these results demonstrate that such custom-designed, food-grade Pickering emulsions provide a promising dietary intervention, with potential to complement or even replace conventional UC therapies.