Bioadhesive polymers as platforms for oral-controlled drug delivery: method to study bioadhesion

To overcome the relatively short gastrointestinal time and improve localization for oral-controlled or sustained-release drug delivery systems, it is suggested that bioadhesive polymers which adhere to the mucin/epithelial surface will be effective and lead to significant improvements in oral drug delivery. Improvements would also be expected for other mucus-covered sites of drug administration. To examine a large number of polymers as to their bioadhesive potential and to derive meaningful information on the structural requirements for bioadhesion a new, simple experimental technique that can quantitatively measure bioadhesive properties of various polymers has been developed. The technique consists of labeling the lipid bilayer of cultured human conjunctival epithelial cells with the fluorescent probe pyrene. Addition of polymers to this substrate surface compresses the lipid bilayer causing a change in fluorescence as compared to control cells. The fluorescent probe, pyrene, provides information on membrane viscosity, which is proportional to polymer binding. In addition to the use of pyrene, membrane proteins were labeled with fluorescein isothiocyanate, and depolarization of probelabeled proteins was measured before and after polymer treatment. By using these fluorescent probes, it was possible to compare charge sign, charge type and density, and backbone structure as to their influence on polymer adhesion. Preliminary comments on structural features for polymer binding are that highly charged carboxylated polyanions are good potential bioadhesives for drug delivery.