Ternary inulin hydrogel with long-term intestinal retention for simultaneously reversing IBD and its fibrotic complication

• Published in: Nature communications 2024-09, Vol.15 (1), p.8428-19, Article 8428
• Main Authors: Cao, Xiangjing, Tao, Shi, Wang, Weitao, Wu, Silong, Hong, Yang, Wang, Xuyuan, Ma, Yan, Qian, Haisheng, Zha, Zhengbao
• Format: Article
• Language: English
• Subjects: 14/32; 14/34; 147/135; 692/4020/1503/257/1389; 692/4020/1503/2745; 692/699/1503/257/1389; Animal models; Animals; Colitis; Colitis - chemically induced; Colitis - drug therapy; Colitis - pathology; Dextran; Dextran Sulfate; Dextrans; Disease Models, Animal; Dysbacteriosis; Fibrosis; Gastrointestinal Microbiome - drug effects; Humanities and Social Sciences; Humans; Hydrogels; Hydrogels - chemistry; Inflammatory bowel disease; Inflammatory bowel diseases; Inflammatory Bowel Diseases - drug therapy; Inflammatory Bowel Diseases - pathology; Intestinal microflora; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Intestine; Intestines - drug effects; Intestines - microbiology; Intestines - pathology; Inulin; Inulin - chemistry; Male; Mice; Mice, Inbred C57BL; Microbiota; Microorganisms; multidisciplinary; Oral administration; Pathophysiology; Polypyrroles; Probiotics; Pyrroles - chemistry; Reactive nitrogen species; Reactive oxygen species; Reactive Oxygen Species - metabolism; Scavenging; Science; Science (multidisciplinary); Signal transduction; Signal Transduction - drug effects; Smad protein; Sodium sulfate; Transforming Growth Factor beta - metabolism; Transforming growth factor-b
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-52722-7

Excessive accumulation of reactive oxygen and nitrogen species (RONS) and dysbiosis of intestinal microbiota are pivotal symptoms for inflammatory bowel disease (IBD) and its associated complications, such as intestinal fibrosis. This research introduces a probiotic inulin hydrogel loaded with polypyrrole (PPy) nanozymes and antifibrotic drug pirfenidone (PFD) (PPy/PFD@Inulin gel) designed for the concurrent amelioration of IBD and its fibrotic complication. Upon oral administration, the inulin gel matrix could extend the gastrointestinal residence time of PPy nanozymes and PFD, facilitating the efficient reduction of pro-inflammatory cytokine levels and enhancement of the intestinal epithelial barrier repair as well as the suppression of intestinal fibrosis through sustained RONS scavenging, modulation of gut microbiota and attenuation of the TGF-β/Smad signaling pathway to inhibit fibroblast proliferation. Notably, the PPy/PFD@Inulin gel demonstrated significant prophylactic and therapeutic efficacy in acute and chronic colitis as well as intestinal fibrosis induced by dextran sodium sulfate (DSS) in mouse models. Thus, the engineered ternary PPy/PFD@Inulin gel offered a pioneered paradigm for simultaneous reversal of IBD and its associated complications, such as intestinal fibrosis, in a single therapeutic regimen. Because of its complex pathophysiology, the management of inflammatory bowel disease as well as its fibrotic complication has become a global challenge. Here, the authors show a probiotic inulin hydrogel loaded with polypyrrole (PPy) nanozymes and antifibrotic drug pirfenidone (PFD) (PPy/PFD@Inulin gel) designed for the concurrent amelioration of IBD and its fibrotic complication.