Release and Targeting Mechanism of Nanomedicine Delivery System in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), arises from multifactorial pathogenesis involving colonic barrier dysfunction, gut microbiota dysbiosis, and aberrant immune regulation. The complexity of these mechanisms poses substantial challenges to achieving curative outcomes, necessitating long-term maintenance therapies. Conventional therapeutic agents (5-aminosalicylic acids, glucocorticoids, immunosuppressants, and biologics) are constrained by inherent limitations including poor solubility, chemical instability, non-specific biodistribution, and off-target toxicity, which collectively compromise therapeutic efficacy and safety. To address these challenges, nanomaterial drug delivery systems (NDDS) have emerged as a transformative strategy to enhance drug solubility, achieve spatiotemporal control, and improve intestinal targeting while reducing systemic exposure. Building upon our prior review that established a taxonomy of NDDS, this review outlines the in vivo delivery mechanisms of nanomedicine delivery systems for IBD, with the organic integration of drug-loading strategies, drug administration routes, stimulus-responsive release, and targeting mechanisms as the core framework. By systematically integrating these multidimensional mechanisms throughout the entire drug administration lifecycle, this review constructs a theoretical framework that combines macroscopic vision with mechanistic depth, laying the foundation for the rational design of next-generation intelligent NDDS and providing systematic theoretical support for improving the treatment efficacy of IBD, minimizing systemic toxicity, and promoting the clinical translation of NDDS.