Mesoporous catechin hydrogel for enhanced astaxanthin-based inflammatory bowel disease therapy

Inflammatory bowel disease (IBD) is a persistent intestinal inflammation driven by epithelial barrier dysfunction, immunological imbalance, and microbial dysbiosis. The restoration of gut homeostasis through biomaterial-based strategies offers a potential avenue for alleviating inflammation in IBD. Herein, an alginate-based hydrogel incorporating astaxanthin-loaded mesoporous catechin nanoparticles (AST@MCN-Gel) was designed to relieve inflammation and rebalance gut homeostasis. The mesoporous framework of MCN enabled effective encapsulation of the hydrophobic AST, thereby increasing its water solubility and bioavailability. In lipopolysaccharide-induced macrophages, AST@MCN exhibited superior ROS-scavenging capacity and anti-inflammatory activity relative to either AST or MCN. Mechanistically, AST@MCN modulated macrophage phenotype from pro-inflammatory (M1) to anti-inflammatory (M2) state through regulation of the MAPK/NF-κB pathway. On the other hand, the alginate-based hydrogel effectively enhanced the intestinal retention of AST@MCN, resulting in a marked improvement in oral therapeutic efficacy. In a DSS-induced IBD mouse model, oral administration of AST@MCN-Gel significantly alleviated the clinical symptoms and restored intestinal barrier integrity. Analysis of the gut microbiome further indicated that AST@MCN-Gel ameliorated gut dysbiosis by restoring microbial diversity and suppressing the proliferation of pathogenic species. Collectively, these underscore the potential of AST@MCN-Gel as an effective biomaterial-based therapeutic approach for restoring intestinal homeostasis and improving IBD therapy.