Amelioration of Colitis Using Colonic Microbiota-Stimulated Release of Tributyrin from Pickering Emulsion-Filled Alginate Beads

Oral administration of tributyrin, a prodrug of butyrate, to the colon is challenging due to its unpleasant odor, rapid metabolism, and fast absorption within the upper gastrointestinal tract. In this study, the colon-targeted delivery of tributyrin was investigated using Pickering emulsion-filled alginate hydrogel beads. Initially, a tributyrin-loaded oil-in-water Pickering emulsion was formed, containing oil droplets coated with chitin nanofibers and zein colloid nanoparticles. These droplets were then encapsulated within the biopolymer network of calcium alginate beads. The potential of these structured delivery systems to control the release of tributyrin was assessed by using a simulated gastrointestinal tract, anaerobic fecal fermentation, and intestinal accumulation studies. The ability of the encapsulated tributyrin to ameliorate dextran sulfate sodium-induced colitis was evaluated. The Pickering emulsion-filled hydrogel beads retained their integrity under-simulated upper gastrointestinal tract conditions, leading to superior resistance against tributyrin hydrolysis by lipase compared to Pickering emulsions. During fecal fermentation, hydrogel beads were gradually eroded as a result of intestinal microbiota action, resulting in a sustained release of tributyrin over 48 h and a significant enhancement of butyrate levels (2.35 times at 4 h) in the cecum in a rat study. Tributyrin-loaded hydrogel beads appreciably reduced the secretion of pro-inflammatory cytokines, thereby relieving symptoms associated with colitis. In the future, it would be useful to test these tributyrin-loaded delivery systems in clinical trials to assess their potential for the treatment of colitis.