Reductase-Labile Peptidic Supramolecular Hydrogels Aided in Oral Delivery of Probiotics

Oral delivery of probiotics has beena promising methodfor treatmentof inflammatory bowel diseases (IBDs). However, probiotics alwayssuffer from substantial loss of viability due to the harsh gastrointestinalconditions, especially the highly acidic environment in the stomachand bile salts in the intestine. In addition, to overcome the challengingconditions, an ideal delivery of probiotics requires the on-demandrelease of probiotics upon environmental response. Herein, a novelnitroreductase (NTR) labile peptidic hydrogel based on supramolecularself-assembly is demonstrated. The efficient encapsulation of typicalprobiotic Escherichia coli Nissle 1917 (EcN) into supramolecular assemblies yieldeda probiotic-loaded hydrogel (EcN@Gel). Such a hydrogel adequatelyprotected EcN to improve its viability against harsh acid and bilesalt environments during oral delivery. The upregulated NTR in theintestinal tract triggered the disassembly of the hydrogel and accomplishedthe controlled release of EcN locally. In ulcerative colitis (UC)-bearingmice, EcN@Gel showed significantly enhanced therapeutic efficacy bydownregulating proinflammatory cytokines and repairing the intestinalbarrier. Moreover, EcN@Gel remolded the gut microbiome by increasingthe diversity and abundance of indigenous probiotics, contributingto ameliorated therapies of IBDs. The NTR-labile hydrogel provideda promising platform for the on-demand delivery of probiotics intothe intestinal tract.

Automated summary

This article presents a novel nitroreductase (NTR) labile peptidic hydrogel based on supramolecular self-assembly for the delivery of probiotics to the intestinal tract. The hydrogel effectively protects probiotics against harsh gastrointestinal conditions, and can be triggered to release probiotics by upregulated NTR in the intestine. The probiotic-loaded hydrogel shows enhanced therapeutic efficacy in an ulcerative colitis model by reducing proinflammatory cytokines and promoting intestinal barrier repair. Additionally, the hydrogel remodels the gut microbiome by increasing the diversity and abundance of indigenous probiotics, contributing to improved therapies for inflammatory bowel diseases.