Colonic Submucosa Targeted Delivery of Probiotic and Rhein for Ulcerative Colitis Treatment

Abstract Ulcerative colitis (UC) is a chronic disease. A significant challenge for the management of UC is to achieve delivery of drugs to the multi‐layer colonic barriers, as existing drugs are difficult to penetrate these depths. In this study, a novel drug delivery system using yeast cell wall microparticles (YPs) are developed to co‐encapsulate Bacillus subtilis (BS) and Rhein (Rh) termed Rh‐YBS. This system specifically targets colonic microfold cells, enabling direct delivery of BS to the colonic submucosa. Additionally, Rh enhances BS colonization in the submucosa through floral regulation. Studies indicate that Rh‐YBS can effectively reach and proliferate within the submucosa in vivo. In a DSS‐induced UC mouse model, Rh‐YBS stimulates the CGRP‐related neural pathway; BS activation in the submucosa leads to increased CGRP secretion, prompting goblet cells to secrete mucus and thereby repairing the mucosa. Furthermore, the Rh‐YBS also provide a preventive benefit against UC. In summary, Rh‐YBS represents an innovative drug delivery system for mucosal repair in UC treatment, activating a unique mechanism involving the CGRP‐related neural pathway.