Molecular aspects of muco- and bioadhesion: tethered structures and site-specific surfaces

Mucoadhesive controlled-release devices can improve the effectiveness of a drug by maintaining the drug concentration between the effective and toxic levels, inhibiting the dilution of the drug in the body fluids, and allowing targeting and localization of a drug at a specific site. Acrylic-based hydrogels have been used extensively as mucoadhesive systems. They are well suited for bioadhesion due to their flexibility and nonabrasive characteristics in the partially swollen state, which reduce damage-causing attrition to the tissues in contact. Crosslinked polymeric devices may be rendered adhesive to the mucosa. For example, adhesive capabilities of these hydrogels can be improved by tethering of long flexible chains to their surfaces. Tethering of long poly(ethylene glycol) (PEG) chains on poly(acrylic acid) hydrogels and their copolymers can be achieved by grafting reactions, or by copolymerization in the presence of several PEG-containing acrylates. The ensuing hydrogels exhibit mucoadhesive properties due to enhanced anchoring of the chains with the mucosa. Theoretical calculations can lead to optimization of the tethered structure. Experimental results indicate that the chain interpenetration is a strong function of the PEG molecular weight, the polymer swelling ratio and the mucosa composition.