Eliminating ROS and Alleviating Inflammation to Restore the Integrity of Intestinal Epithelium in DSS-Induced Ulcerative Colitis by a pH-Responsive Delivery System of Curcumin

The current consensus is that combating reactive oxygen species (ROS) and implementing site-specific drug delivery are effective strategies for managing ulcerative colitis (UC). Herein, ferulic acid (FA) was used to fabricate curcumin (CUR) derivative polymer nanoparticles (CURDNPs) as a delivery vehicle for CUR, forming CURDNPs@CUR. This system enhances the dispersion, bioavailability, UV protection, and controlled-release performance of CUR while also improving its ROS-eliminating activity. In dextran sulfate sodium salt (DSS)-treated mice, CURDNPs@CUR delivers curcumin specifically to the colon, boosts antioxidant enzyme activity, and significantly ameliorates colon histopathology. It reduces the expression of pro-inflammatory cytokine genes (TNFα, NLRP3, and iNOS) and restores intestinal epithelial integrity by decreasing intestinal permeability and enhancing the expression of tight junction proteins (TJPs), including ZO-1, Occludin-1, and Claudin-1. These findings suggest the successful synthesis of a targeted/antioxidant CUR delivery vehicle for synergistic UC therapy via ROS elimination, barrier repair, and anti-inflammation.