Probiotic-drug co-delivery system enhances sulfasalazine activation for inflammatory bowel disease therapy

Inflammatory bowel disease (IBD), affecting millions of patients worldwide, is associated with mucosal inflammation and gut microbiota dysbiosis. As a prodrug of 5-aminosalicylic acid (5-ASA), sulfasalazine (SSZ) is a first-line medication for IBD. However, SSZ exhibits limited clinical efficacy due to its nonspecific systemic distribution and the inefficient cleavage of the azo bond, which results from inadequate azo reductase (AR) activity. Intriguingly, we found that Clostridium butyricum (CB) possess AR activity and can metabolize SSZ into 5-ASA. Here, we develop a pH and enzyme dual-responsive drug delivery system CBs/SSZ/CS/EudS-100 by encapsulating the SSZ-loaded Clostridium butyricum spore (CBs) with chitosan (CS) and Eudragit S100 (EudS-100). After oral administration, it is identified that the CS and EudS-100 coating enables the colonic release of SSZ. On the one hand, CBs germinates into CB, which facilitates the conversion of SSZ to 5-ASA, relieving inflammation and repairing intestinal barrier. On the other hand, CB modulates the disordered gut microbiota. This provides a new strategy for integrating probiotic therapy with pharmacological treatment in the management of IBD.