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Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans
KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Chem, Div Glycosci, Stockholm, Sweden.ORCID iD: 0000-0001-7800-3533
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Chem, Div Glycosci, Stockholm, Sweden.
KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Chem, Div Glycosci, Stockholm, Sweden.
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2018 (English)In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 19, no 3, p. 872-882Article in journal (Refereed) Published
Abstract [en]

The mucus gel covers the wet epithelia that forms the inner lining of the body. It constitutes our first line of defense protecting the body from infections and other deleterious molecules. Failure of the mucus barrier can lead to the inflammation of the mucosa such as in inflammatory bowel diseases. Unfortunately, there are no effective strategies that reinforce the mucus barrier properties to recover or enhance its ability to protect the epithelium. Herein, we describe a mucus engineering approach that addresses this issue where we physically cross-link the mucus gel with low molar mass chitosan variants to reinforce its barrier functions. We tested the effect of these chitosans on mucus using in-lab purified porcine gastric mucins, which mimic the native properties of mucus, and on mucus-secreting HT29-MTX epithelial cell cultures. We found that the lowest molar mass chitosan variant (degree of polymerization of 8) diffuses deep into the mucus gels while physically cross-linking the mucin polymers, whereas the higher molar mass chitosan variants (degree of polymerization of 52 and 100) interact only superficially. The complexation resulted in a tighter mucin polymer mesh that slowed the diffusion of dextran polymers and of the cholera toxin B subunit protein through the mucus gels. These results uncover a new use for low molar mass mucoadhesive polymers such as chitosans as noncytotoxic mucosal barrier enhancers that could be valuable in the prevention and treatment of mucosal diseases.

Place, publisher, year, edition, pages
AMER CHEMICAL SOC , 2018. Vol. 19, no 3, p. 872-882
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Physical Chemistry Engineering and Technology
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URN: urn:nbn:se:uu:diva-351093DOI: 10.1021/acs.biomac.7b01670ISI: 000427539600017PubMedID: 29451983OAI: oai:DiVA.org:uu-351093DiVA, id: diva2:1208730
Funder
Swedish Research Council, 2014-6203]Available from: 2018-05-18 Created: 2018-05-18 Last updated: 2018-06-05Bibliographically approved

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Kootala, SujitFilho, Luimar

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