Advances in Pharmacotherapeutic Strategies for Functional Gastrointestinal Disorders: Nanotechnology-Based Approaches and Future TherapeuticFrontiers

Introduction: Functional gastrointestinal disorders (FGIDs), including IBS, FD, and GERD, represent complex clinical entities characterized by the convergence of gut-brain axis dysfunction, aberrant visceral pain processing, immune activation, and microbial dysbiosis, leading to persistent gastrointestinal symptoms despite the absence of identifiable structural changes. Traditional pharmacological strategies, including antacids, proton pump inhibitors (PPIs), antispasmodics, prokinetics, and neuromodulators, often provide only partial relief and may cause adverse effects. Methodology: This review aimed to compile current pharmacological strategies and recent innovations, focusing on nanotechnology-based drug delivery systems, biologics, gene therapies, and microbiome-targeted interventions. Key preclinical and clinical findings were analyzed to assess therapeutic efficacy and the innovation of delivery strategies. Results: Recent advances have introduced biologics and nanotechnology-based drug delivery systems as promising therapies for FGIDs. Nanoparticles, such as lipid, polymeric, and inorganic types, offer improved drug stability, bioavailability, and site-specific delivery. Novel formulations, including ROS-responsive and mucus-penetrating particles, enable controlled, inflammation- targeted release with reduced toxicity. Functional agents, such as curcumin, berberine, and TNF-α siRNA, exhibit enhanced efficacy in preclinical IBD models when delivered via nanoparticles. Additionally, microbiome-based therapies, such as probiotics, synbiotics, and fecal microbiota transplantation, support modulation of the gut-brain axis and restoration of microbial balance. Discussion: Therapeutic approaches are shifting from symptomatic management to targeted and mechanism-based strategies. Precision medicine incorporating genomic, proteomic, and microbiome profiling offers the potential for personalized treatments. Conclusion: Emerging therapies, particularly NP-based systems and microbiome-centered interventions, offer a transformative potential in FGID management. However, challenges in regulatory, accessibility, and combination therapy validation must be addressed for clinical translation.