An olsalazine nanoneedle-embedded inulin hydrogel reshapes intestinal homeostasis in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic and refractory condition characterized by disrupted epithelial barrier, dysregulated immune balance, and altered gut microbiota. Nano-enabled interventions for restoring gut homeostasis have the potential to alleviate inflammation in IBD. Herein, we developed a combination of olsalazine (Olsa)-based nanoneedles and microbiota-regulating inulin gel to reshape intestinal homeostasis and relieve inflammation. The Olsa-derived nanoneedles exhibited reactive oxygen species scavenging ability and anti-inflammatory effects in lipopolysaccharide-simulated macrophages. The composite of nanoneedles and inulin gel (Cu2(Olsa)/Gel) displayed a macroporous structure, improved bio-adhesion, and enhanced colon retention after oral administration. Mechanistically, the composite effectively downregulated pro-inflammatory cytokine levels and promoted epithelial barrier repair through anti-inflammatory and antioxidant therapies, resulting in significant alleviation of colitis in three animal models of IBD. Furthermore, analysis of gut microbiota revealed that Cu2(Olsa)/Gel treatment increased the diversity of intestinal microflora and decreased the relative abundance of pathogenic bacteria such as Proteobacteria. Overall, this study provides a self-delivering nanodrug and dietary fiber hydrogel composite for IBD therapy, offering an efficient approach to restore intestinal homeostasis.