Factors influencing gel-strengthening at the mucoadhesive-mucus interface.

Mechanical spectroscopy was used to examine some of the factors that may affect mucus gel strengthening: the effect of adding various concentrations of sodium chloride; mucoadhesive polymer molecular weight and its concentration; and the introduction of anionic, cationic and neutral polymers. A reduction in the storage modulus of the mucus/mucoadhesive mixture was observed with the introduction of sodium chloride. A poly(acrylic acid) with a molecular weight of 750 kDa gave the optimum mucus gel strengthening effect relative to other molecular weights. An anionic polymer was found to strengthen the mucus gel much more than a neutral or cationic polymer. It was proposed that the gel strengthening effect could be due to the formation of hydrogen bonded intermolecular complexes between the mucoadhesive and the mucus molecules. Furthermore, the complex formed is influenced by the ionic strength of the environment, and the molecular weight, nature and concentration of the mucoadhesive. In all cases the changes in the rheological properties of the mixes could be correlated directly to the strength of mucoadhesion reported in previous studies.