Antibacterial hyaluronic acid hydrogel with sustained release of larazotide as effective colitis treatment.

This preclinical study developed a dual-crosslinked injectable hydrogel (HSMP-LA) designed to mimic natural gut mucus for treating colitis. The hydrogel combined thiol/maleimide-modified hyaluronic acid with two active agents: antimicrobial ε-polylysine (ε-PL) and larazotide acetate (LA), a tight junction–regulating peptide. In laboratory (in vitro) experiments using LPS-injured Caco-2 intestinal cells, sustained release of LA was reported to selectively inhibit zonulin-mediated tight junction disruption by targeting the MLCK/p-MLC signaling pathway, thereby restoring epithelial barrier integrity. The hydrogel also demonstrated broad-spectrum antimicrobial activity and strong mucoadhesive properties with prolonged retention. In a dextran sodium sulfate (DSS)-induced mouse model of colitis, HSMP-LA significantly reduced disease activity indices, suppressed pro-inflammatory cytokines, upregulated anti-inflammatory IL-10, repaired tight junction proteins (ZO-1, occludin, claudin-5), restored mucus production (MUC2), and rebalanced gut microbiota composition. The study's primary limitations are that all findings are confined to cell culture and animal models, with no human data reported. The dual-action strategy—simultaneously targeting barrier dysfunction and microbial imbalance—represents the authors' proposed innovation, though clinical translation remains undemonstrated.

Why this grade: All efficacy data derive exclusively from DSS-induced mouse colitis models and Caco-2 cell assays, with no human or clinical trial data presented.