Starch as a designable platform for oral drug delivery: From structural modulation to application in inflammatory...

The effective management of inflammatory bowel disease (IBD) remains constrained by a central pharmaceutical challenge: achieving site-specific drug delivery to inflamed colonic mucosa while minimizing systemic exposure. Conventional oral formulations often suffer from off-target release and poor bioavailability, leading to suboptimal efficacy and systemic side effects. This review addresses this challenge by focusing on starch, a natural, biodegradable, and structurally versatile polysaccharide, as a foundational material for engineering intelligent colon-targeted carriers. It examines how the hierarchical architecture and tunable chemistry of starch enable the rational design of delivery systems capable of navigating the gastrointestinal tract. Specifically, it discusses chemical, physical, and enzymatic modification strategies that impart starch-based carriers with microenvironment-responsive behavior and active targeting toward overexpressed receptors. Beyond sophisticated targeting, the review critically analyzes how these designed starch-based oral delivery systems exert multi-mechanistic therapeutic effects, including reinforcing the epithelial barrier, restoring microbial homeostasis, and recalibrating immune responses. By synthesizing recent advances through a "structure-to-function" perspective, this work provides a strategic rationale for developing next-generation starch-based oral platforms aimed at precise, localized, and effective intervention in IBD.