Pickering Emulsion‐Embedded Hydrogel Microbeads: Synergistic Stabilization and Controlled Release of Tributyrin for Colonic Delivery

ABSTRACT Tributyrin (TB), a stable triglyceride prodrug of butyrate, holds immense potential for modulating gut health and managing ulcerative colitis (UC) via dietary intervention. However, its application in functional foods is restricted by its hydrophobicity, gastric instability, and rapid absorption in the upper gastrointestinal tract (GIT). To address these challenges, this study engineered a food‐grade, colon‐specific delivery system based on hierarchical emulsion‐filled hydrogel microbeads. TB was initially stabilized by octenyl succinic anhydride (OSA)‐modified Tartary buckwheat starch to form robust Pickering emulsions (OSP), which were subsequently embedded within a pH‐responsive sodium alginate (SA)/carboxymethyl chitosan (CMCS) composite matrix. The intermolecular polyelectrolyte complexation between SA and CMCS, reinforced by Ca 2+ ‐mediated crosslinking, significantly enhanced the structural integrity and encapsulation efficiency (∼64%) of the microbeads (TB‐OSP@C/S). In vitro digestion kinetics demonstrated that this multi‐compartment architecture acted as an effective diffusion barrier, suppressing gastric release (< 20%) while facilitating sustained release in the simulated colonic environment driven by pH‐dependent swelling and the enzymatic degradation of the protective starch shell. In a DSS‐induced murine colitis model, oral administration of TB‐OSP@C/S microbeads markedly improved the disease activity index, alleviated colonic tissue damage, and exhibited superior anti‐inflammatory efficacy compared to free TB. This work presents a facile, surfactant‐free strategy for the precise delivery of hydrophobic nutraceuticals, offering a promising paradigm for developing precision nutrition products targeting intestinal inflammation.