Mucoadhesive polymers covalent binding

Mucoadhesive polymers can be divided into non-covalent binding and covalent binding polymers. On the one hand the mechanism of mucoadhesion is based on hydrogen bonds, ionic interactions and van der Waal forces for non-covalent binding polymers, and on the other hand, on covalent bonds between the mucus and certain residues of the polymer. Moreover, physical interactions such as interpenetration of the polymer into the mucus gel layer entangle the polymer chains, which is strongly influenced by the swelling behaviour of the... 

If the conventional mucoadhesive polymers were characterized by adhering to the mucin non-spe-cifically and lacking specificity, the new generation of mucoadhesive polymers is characterized by either binding covalently (thiomers) or simply by binding to the cell surface. 

Thiolated polymers, also termed thiomers, are conventional mucoadhesive polymers chemically modified to contain a cysteine residue in the polymer chain and thus establish covalent disulfide bonds with mucin." They can be manufactured to be either cationic (mostly thiolated chitosans) or anionic (carboxylic acid-containing polymers) however, their mucoadhesive extent will mostly be determined by their capacity to covalently bind to mucin. The polypeptide backbone of mucin can be divided into three major subunits tandem repeat array, carboxyl-, and amino-terminal domains. While the amino-terminal domain contains some of the cysteine residues, the carboxyl-terminal domain contains more than 10% of the cysteine residues. These cysteine-rich regions are responsible for forming the large mucin oligomers and ultimately, the groups that allow for the covalent mucoadhesive bond formation with oral mucosal systems." ... 

Contrary to what has been reported for non-covalently binding mucoadhesive polymers, the disulfide bond is not influenced by ionic strength, electrostatic, or hydrophobic domain interactions." The extent of the disulfide bond is strictly related to the concentration of thiolate anions, which is the group that will go through thiol/disulfide exchange reactions and oxidation processes. The concentration of the thiolate groups is mostly determined by the p T value of the thiol group. 

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