Folic acid-based hydrogels co-assembled with protocatechuic acid for enhanced treatment of inflammatory bowel disease

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2025-02, Vol.246, p.114367, Article 114367
• Main Authors: Ye, Ximei, Chen, Tao, Du, Yinan, Zhao, Runan, Chen, Lihang, Wu, Di, Hu, Jiangning
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - chemistry; Antioxidants - pharmacology; Colitis - chemically induced; Colitis - drug therapy; Colitis - pathology; Dextran Sulfate; Disease Models, Animal; Folic acid; Folic Acid - chemistry; Folic Acid - pharmacology; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Hydroxybenzoates - administration & dosage; Hydroxybenzoates - chemistry; Hydroxybenzoates - pharmacology; Inflammatory bowel disease; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - metabolism; Inflammatory Bowel Diseases - pathology; Male; Mice; Mice, Inbred C57BL; Mucosal adhesion; Oxidative Stress - drug effects; Protocatechuic acid
• ISSN: 0927-7765; 1873-4367; 1873-4367
• DOI: 10.1016/j.colsurfb.2024.114367

Inflammatory bowel disease (IBD) presents a significant therapeutic challenge due to the need for oral drug delivery systems that withstand acidic environment of stomach while effectively targeting intestinal inflammation. To address this issue, we created a novel hydrogel system based on a folic acid (FA)-dopamine (DA) conjugate, co-assembled with protocatechuic acid (PCA), to form F-DP hydrogels. These hydrogels demonstrated robust anti-gastric acid, mucosal adhesive, and injectable properties, enhancing their efficacy for targeted delivery. In DSS-induced colitis mouse models, treatment with F-DP hydrogels resulted in significant therapeutic improvements, including increased body weight, reduced disease activity index (DAI), and maintained colon length. Biochemical assays revealed that F-DP hydrogels significantly enhanced antioxidant enzyme activities (GSH and SOD) and reduced oxidative stress markers (NO and MDA). Histological assessments confirmed effective repair of the colonic mucosal barrier, restoration of tight junction protein ZO-1, and reduction of inflammatory lesions. Furthermore, immunofluorescence staining indicated that F-DP hydrogels facilitated macrophages polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, thereby reducing inflammation and promoting tissue repair. Our study demonstrates that F-DP hydrogels show significant potential for improving IBD treatment through enhanced gastric resistance, intestinal adhesion, and synergistic anti-inflammatory effects, warranting further investigation for clinical applications. •The modified F-DP hydrogels can effectively withstand the erosion of the gastrointestinal environment and smoothly reach the colon.•The F-DP hydrogels possesses outstanding specific bioadhesion to colon inflammatory tissues.•The F-DP hydrogels alleviated the oxidative damage and inflammatory response of RAW264.7 cells.•Oral administration of F-DP hydrogels mitigated colonic inflammation in IBD mice by repairing intestinal mucosal damage and promoting macrophage polarization.