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

Xiangjing Cao, Shi Tao, Weitao Wang, Silong Wu, Yang Hong, Xuyuan Wang, Yan Ma (), Haisheng Qian () and Zhengbao Zha ()
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Xiangjing Cao: Hefei University of Technology
Shi Tao: Hefei University of Technology
Weitao Wang: Hefei University of Technology
Silong Wu: Anhui Medical University
Yang Hong: Hefei University of Technology
Xuyuan Wang: Anhui Medical University
Yan Ma: Anhui Medical University
Haisheng Qian: Anhui Medical University
Zhengbao Zha: Hefei University of Technology

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-52722-7

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