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Bioorthogonal conjugation and responsive nanocoating of probiotics for inflammatory bowel disease.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Oct; Vol. 374, pp. 538-549. Date of Electronic Publication: 2024 Aug 30. - Publication Year :
- 2024
-
Abstract
- Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest.<br /> (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Gastrointestinal Microbiome
Mice
Escherichia coli drug effects
Colitis chemically induced
Colitis therapy
Humans
Immunologic Factors administration & dosage
Male
Cytokines metabolism
Administration, Oral
RAW 264.7 Cells
Intestinal Mucosa metabolism
Macrophages drug effects
Probiotics administration & dosage
Inflammatory Bowel Diseases therapy
Mice, Inbred C57BL
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 374
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 39186984
- Full Text :
- https://doi.org/10.1016/j.jconrel.2024.08.036