**2.6 Mucoadhesive systems**

Mucoadhesive systems utilize the bioadhesive phenomenon where certain components of the system (usually a polymer) form adhesion bonds with the mucosal membrane at the absorption site. This adhesion may lead to a high concentration of the therapeutic molecule, which increases absorption of the therapeutic molecule. Adhesion of the polymer in the delivery system also leads to an increase the residence time of the therapeutic molecule at the site of absorption and thus, further enhances the absorption and the bioavailability of the therapeutic agent [55].

The properties of the mucoadhesive system depends on the nature of the polymer used. The polymer should be hydrophilic enough to properly interact with the high amount of water present in the mucus layer. The polymer should be large enough (high molecular weight) to increase the possibility of interactions. The polymer should also have proper surface tension to allow the spreading of the polymer on the mucus layer. The polymer should contain functional groups (e.g., COOH, OH, etc.) to form strong H-bonds. Finally, the polymer should be non-toxic and non-immunogenic [41]. Although the main function of polymer in mucoadhesive drug delivery system is to form adhesive bonds with the mucus membrane to enhance the bioavailability of the protein or peptide, some polymers may have additional functions. For example, some polymers can act as absorption enhancers

by modifying tight junctions between epithelial cells and by inhibiting proteases that hydrolyze proteins or peptides [56].

Cellulose derivatives (e.g., methylcellulose, hydroxyethyl cellulose, carboxymethyl cellulose) are used in mucoadhesive drug delivery systems. Other commonly used polymers are polyacrylic acid derivatives such as carbapol and polyacrylate. Thiol-containing polymers are also used in mucoadhesive systems. These polymers show strong adhesive binding with the mucus layer due to the formation of covalent bonds in addition to the non-covalent interactions. The thiol group in these polymers forms disulfide bonds with the cysteine residues present in the glycoproteins of the mucus. It has been reported that the increase in the thiol group in the polymer increases the strength of adhesive binding [23].
