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Oral antimicrobial peptide-EGCG nanomedicines for synergistic treatment of ulcerative colitis.

Authors:
Shengsheng Liu Yingui Cao Lingli Ma Jianfeng Sun Lorenzo Ramos-Mucci Ya Ma Xiao Yang Zhenhua Zhu Jianxiang Zhang Bo Xiao

J Control Release 2022 Jul 25;347:544-560. Epub 2022 May 25.

State Key Laboratory of Silkworm Genome Biology, College of Sericulture, Textile, and Biomass Sciences, Southwest University, Beibei, Chongqing 400715, China; Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Beibei, Chongqing 400715, China. Electronic address:

The pathogenesis of ulcerative colitis (UC) is associated with severe inflammation, damaged colonic barriers, increased oxidative stress, and intestinal dysbiosis. The majority of current medications strive to alleviate inflammation but fail to target additional disease pathologies. Addressing multiple symptoms using a single 'magic bullet' remains a challenge. To overcome this, a smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticle (NP) with the surface functionalization of antimicrobial peptides (Cathelicidin-BF, CBF) was constructed, which could be internalized by Colon-26 cells and RAW 264.7 macrophages with high efficiencies. The resulting CBF-EGCG-NPs efficiently restored colonic epithelial barriers by relieving oxidative stress and promoting epithelium migration. They also alleviated immune responses through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and lipopolysaccharide (LPS) elimination. Interestingly, oral administration of hydrogel (chitosan/alginate)-embedding CBF-EGCG-NPs could not only retard progression and treat UC, but also modulate intestinal microbiota by increasing their overall diversity and richness and augmenting the abundance of beneficial bacteria (e.g., Firmicutes and Lactobacillaceae). Our work provides a "many birds with one stone" strategy for addressing UC symptoms using a single NP-based oral platform that targets immune microenvironment modulation, LPS clearance, and microbial remodeling.

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http://dx.doi.org/10.1016/j.jconrel.2022.05.025DOI Listing
July 2022

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