Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans

粘液 粘蛋白 摩尔质量 化学 壳聚糖 右旋糖酐 生物物理学 分子质量 聚合物 生物化学 生物 有机化学 生态学
作者
Sujit Kootala,Luimar Filho,Vaibhav Srivastava,Victoria Linderberg,Amani Moussa,Laurent David,Stéphane Trombotto,Thomas Crouzier
出处
期刊:Biomacromolecules [American Chemical Society]
卷期号:19 (3): 872-882 被引量:27
标识
DOI:10.1021/acs.biomac.7b01670
摘要

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.
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