Gut-active polysaccharide carriers for colonic 5-ASA delivery in ulcerative colitis

Ulcerative colitis (UC) affects approximately 4.9 million people worldwide, with incidence rising globally and prevalence approaching 1% in industrialized nations. 5-Aminosalicylic acid (5-ASA) is first-line therapy for mild-to-moderately active UC, yet pooled endoscopic mucosal healing averages only approximately 37% and 10-year relapse approaches 67%. A central reason is ineffective drug delivery: current technologies release 5-ASA into the bulk lumen, and pH-dependent coatings fail in active UC, where intracolonic pH is variable. Mucosal tissue concentration, not luminal concentration, determines efficacy, and concurrent gut dysbiosis sustains inflammation that current 5-ASA formulations fail to address.

UC-associated gut dysbiosis, the limitations of current colonic 5-ASA delivery, and gut-active polysaccharide carriers (inulin and modified inulin, pectin, guar gum, konjac glucomannan [KGM], resistant starch, and hyaluronic acid [HA]) applied specifically to 5-ASA. Advanced nanoparticle and hydrogel platforms and translational and regulatory priorities are also discussed.

Gut-active, enzyme-responsive polysaccharide carriers are a rational formulation strategy for UC. By coupling colonic 5-ASA release to microbial fermentation at the mucosal interface, they deliver drug closer to the epithelial target while generating short-chain fatty acids (SCFA) that may attenuate dysbiosis. Since release is enzyme-triggered rather than pH-dependent, these systems can overcome the dissolution failure that limits current 5-ASA delivery.