Chitosan-montmorillonite composite protects the intestinal barrier in DSS-induced colitis mice by modulating tight junctions and the TLR4/NF-κB pathway

Ulcerative colitis (UC), a subtype of inflammatory bowel disease (IBD), is characterizted by mucosal inflammation and the impaired epithelial barrier integrity. Montmorillonite (MMT), a layered aluminosilicate, could partially restored intestinal barrier function in UC patients but showed limited efficacy in preventing disease relapse and alleviating acute inflammatory flares in UC patients. This study we developed a chitosan (CS) and MMT intercalation compound (CM), which synergistically combines the benefits of both components. CM was synthesized using solution intercalation method and explored the mechanism. FTIR and SEM confirmed the successful intercalation of CS into the MMT layers, which was further supported by XRD (disappearance of the 7.163° peak), TGA (74% residual mass at 800 °C), and zeta potential (−7.43 mV). In cell and animal models, CM treatment significantly prevented mucosal damage and suppressed inflammatory responses. Mechanismly, CM could down regulate TLR4 expression and inhibit the activation of the NF-κB, leading to reduced levels of pro-inflammatory cytokines, such as IL-1β, IL-6, TNF-α and IFN-γ. Meanwhile, CM could up regulate the expression of the tight junction proteins, which could maintain mucosal integrity. CM-FITC enrichment studies confirmed preferential colonic accumulation. Give the low cost, biocompatibility and scalable synthesis of chitosan and montmorillonite, CM represents a promising therapeutic adjuvant for UC prevention and treatment.