abstract

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract characterized by disruption of intestinal homeostasis, epithelial barrier dysfunction, immune dysregulation, oxidative stress, and alterations in the gut microbiome. Although currently available therapies can effectively control disease activity in many patients, limitations associated with systemic exposure, incomplete response, adverse effects, and inadequate localization of therapeutic agents continue to motivate the development of targeted drug-delivery systems. The present study investigated the therapeutic potential of an optimized microbiome- and reactive oxygen species (ROS)-responsive nanocarrier developed for targeted delivery of a selected therapeutic drug in experimental IBD. Following characterization of the optimized formulation, its therapeutic performance was evaluated using an appropriate experimental model of intestinal inflammation. Animals were allocated into appropriate treatment and control groups, and disease activity was assessed using relevant clinical and physiological parameters. Histopathological examination was performed to determine structural changes in intestinal tissues. Oxidative stress and antioxidant defence were evaluated using appropriate biochemical biomarkers, while inflammatory responses were assessed through relevant cytokine measurements. Gut microbiome profiling was performed to investigate treatment-associated changes in microbial composition and/or function. Biodistribution and pharmacokinetic studies were undertaken to evaluate tissue targeting and drug exposure, while safety and toxicological parameters were assessed to determine tolerability. The overall research framework was designed to examine the interconnected relationship among nanocarrier-mediated drug delivery, microbiome modulation, oxidative stress reduction, inflammatory control, and improvement in intestinal pathology. The study provides a preclinical framework for evaluating dual-responsive nanomedicine as a potential targeted therapeutic strategy for IBD.