Reinforcing Mucus Barrier Properties with Low Molar Mass Chitosans

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.