FROM STICKY STUFF TO SWEET RECEPTORS - ACHIEVEMENTS, LIMITS AND NOVELAPPROACHES TO BIOADHESION

About 10 years ago, the concept of bioadhesion was introduced into the pharmaceutical literature and has since stimulated much research and development both in academia and in industry. The first generation of bioadhesive drug delivery systems (BEDS) were based on so-called mucoa dhesive polymers, i.e. natural or synthetic macromolecules, often alre ady well accepted and used as pharmaceutical excipients for other purp oses, which show the remarkable ability to 'stick' to humid or wet muc osal tissue surfaces. While these novel dosage forms were mainly expec ted to allow for a possible prolongation, better localization or inten sified contact to mucosal tissue surfaces, it had to be realized that these goals were often not so easily accomplished, at least not by mea ns of such relatively straightforward technology. However, although no t always convincing as a 'pharmaceutical glue', some of the mucoadhesi ve polymers were found to display other, possibly even more important biological activities, namely to inhibit proteolytic enzymes and/or to modulate the permeability of usually tight epithelial tissue barriers . Such features were found to be particularly useful in the context of peptide and protein drug delivery. But still, the interest in realizi ng 'true' bioadhesion continues: instead of mucoadhesive polymers, pla nt or bacterial lectins, i.e adhesion molecules which specifically bin d to sugar moieties of the epithelial cell membrane, are now widely be ing investigated as drug delivery adjuvants. These second-generation b ioadhesives not only provide for cellular binding, but also for subseq uent endo- and transcytosis. This makes the novel, specifically bioadh esive molecules particularly interesting for the controlled delivery o f DNA/RNA molecules in the context of antisense or gene therapy.