Explants from the small intestine of CF mice were mounted in the horizontal Ussing-type chamber. Alginate at different concentrations or composition was added to the apical buffer, pH 7.4. The attachment of the already formed mucus was assessed by comparing the total mucus thickness before and after aspiration.
OligoG at 1.5% or higher normalized the mucus phenotype without increase in mucus thickness. The alginate fraction containing 12 guluronate units was most effective, whereas shorter and longer molecules were less efficient. Mannuronic polymers were inactive.
These results suggest that it is guluronic acid and its calcium chelating capacity that is the important and active component in OligoG. These observations indicate that OligoG could act by normalizing the mucus layers in both the intestine and potentially the lungs of cystic fibrosis patients at therapeutically relevant concentrations.