Fabrication of Colon-Targeted Delivery System of Astaxanthin Based on Bacteroides-Dependent Biodegradation Strategy and Its Role in Ameliorating DSS-Induced Colitis in Mice

Astaxanthin (Ax) is a potent antioxidant, yet its poor water solubility and instability limit its application. While alginate-Ca encapsulation protects Ax during digestion, its release in the colon is often inefficient. This study aims to optimize colon-targeted delivery by integrating inulin and fucoidan, which respond selectively to Bacteroides-mediated fermentation. A novel delivery system was developed using Ax-containing particles formulated in an alginate–inulin–fucoidan matrix (Ax-Mix), with most particles ranging from 2 to 20 μm. In vitro results showed that the incorporation of inulin and fucoidan enhanced Ax release in alginate-Ca (Ax-Alg) through Bacteroides fermentation. Ax-Mix exhibited robust structural integrity under varying pH, thermal, and ionic conditions. Ax-Mix remained intact through the oral cavity, stomach, and small intestine, but disintegrated in the colon, triggering Ax release. Ax-Mix alleviated colitis in mice, characterized by increased weight gain and colon length and reduced disease activity index, tissue damage, and oxidative stress. Ax-Mix reshaped the gut microbiota by increasing microbial diversity and enriching beneficial taxa linked to colitis improvement. These alterations resulted in increased propionate and butyrate production. Compared to Ax-Alg, Ax-Mix exhibited superior therapeutic effects on colitis, though the underlying mechanisms require further investigation. This study presents a promising strategy for microbiota-targeted delivery of active substances.