Peptide-based therapeutic and delivery strategies for inflammatory bowel disease: challenges and future directions.

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), remains a challenging chronic disorder with complex pathophysiology and limited therapeutic options. Peptide-based therapeutics have emerged as promising alternatives, offering high specificity, favorable safety profiles, and unique biological activities compared to traditional treatments. However, challenges including enzymatic degradation, poor oral bioavailability, and instability hinder their clinical translation. This review provides a comprehensive overview of the sources, structures, and mechanisms of therapeutic peptides for IBD management. We further discuss recent advances in delivery strategies, including PEGylation, nanoparticle (NP) systems (chitosan (CS), hyaluronic acid (HA), PLGA, lipid-based carriers, polydopamine (PDA), mesoporous materials), hydrogels, engineered probiotics, and montmorillonite-based composites. Particular emphasis is placed on the role of biomaterials in enhancing peptide stability, targeting specificity, and mucosal adhesion. Key challenges-such as optimizing peptide design, ensuring biosafety, refining delivery systems, and improving preclinical models-are critically analyzed. Prospects suggest that combining smart delivery technologies with data-driven peptide engineering will significantly advance peptide-based therapies for precision IBD management.