Orally Administrated Precision Nanomedicine for Restoring the Intestinal Barrier and Alleviating Inflammation in Treatment of Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) presents a significant challenge in healthcare, characterized by its chronicity and complex pathogenesis involving genetic, immune, and environmental factors. Current treatment modalities, including anti-inflammatory drugs, immunomodulators, and biologics, often lack sufficient efficacy and are accompanied by adverse effects, necessitating the urgent search for therapeutic approaches targeting mucosal barrier restoration and inflammation modulation. Precision nanomedicine emerges as a promising solution to directly address these challenges. This study introduces the development of a targeted sequential nanomedicine for precise IBD treatment. This innovative formulation combines a prodrug carrier containing quercetin to restore intestinal barrier integrity through the regulation of tight junctions and an anti-inflammatory agent dexamethasone acetate to alleviate inflammation. Surface modification with pectin enables colon-specific drug delivery, facilitated by degradation by colon-specific microbiota. Responsive drug release, controlled by reactive oxygen species-sensitive chemical bonds within the carrier, ensures both spatial and temporal accuracy. In vitro and in vivo investigations confirm the nanomedicine's favorable physicochemical properties, release kinetics, and therapeutic efficacy, elucidating potential underlying mechanisms. Oral administration of the nanomedicine shows promising results in restoring intestinal barrier function, reducing inflammation, and modulating the gut microbiota. Consequently, this study presents a promising nanomedicine candidate for advancing IBD treatment paradigms.