Multi-modal therapeutic approaches to inflammatory bowel disease: plant-derived compounds, nanoparticle drug delivery systems, and gene-based interventions.

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder primarily affecting the gastrointestinal tract. The pathogenesis arises from complex interactions among genetic predisposition, immune dysregulation, and gut microbiota alterations. Recent advances in molecular biology, genomics, and microbiome research have identified novel therapeutic targets, enabling the development of innovative treatment strategies. Natural products derived from plants offer bioactive compounds with anti-inflammatory, antioxidant, and immunomodulatory properties, gaining attention for IBD symptom management. Conventional therapeutic management includes aminosalicylates, immunomodulators, corticosteroids, and biologics; however, 30-50% of patients show inadequate response, and oral drug delivery faces challenges due to gastrointestinal environmental heterogeneity. Recent years have witnessed substantial advances in nanoparticle-based drug delivery systems for IBD, offering improved targeting capabilities, enhanced therapeutic efficacy, and better tolerability through stimuli-responsive platforms (ROS-sensitive, pH-responsive) and active targeting strategies. Nanoparticle-mediated gene therapy, including siRNA, miRNA, and emerging CRISPR-based approaches, represents a paradigm-shifting strategy for modulating aberrant gene expression in IBD. This comprehensive review synthesizes the current understanding of IBD pathophysiology, evaluates both conventional and emerging therapeutic approaches, and provides critical analysis of advanced nanoparticle delivery systems and gene-based therapeutic strategies.