The aim of this study was to add knowledge to the existing theories of mucoadhesion and to review mucoadhesive polymers based on their ability to form non-covalent bonds with mucus glycoprotein. Resonant mirror biosensor was used to study the candidate mucoadhesive polymers hydroxypropyl methylcellulose, carboxymethylcellulose, Carbopol, hyaluronate, alginate and chitosan. Bovine submaxillary mucin was chosen as substrate, representing the major glycosylated protein in mucus. For comparison, non-glycosylated bovine serum albumin was used as an alternative substrate. The results of this study reveal that there is a clear correlation between the ionization state of the polymer, which is dependent on the pH of the surrounding environment, and its binding behavior. Ionizable polymers need to be in their unionized state to be able to form non-covalent bonds with mucus glycoprotein. Acidic polymers display binding behavior only at pH around or lower than their corresponding pK(a) values and basic polymers vice versa. Chitosan was found to be the most mucoadhesive polymer. Unionizable polymers like hydroxypropyl methylcellulose did not display any affinity for mucus glycoprotein. Unionized amino- and carboxyl groups on polymers were found to be important structural feature of polymer for the formation of weak chemical bonds to mucus glycoproteins.