Lectin-mediated drug delivery: The second generation of bioadhesives

This paper reviews some recent developments in the area of bioadhesive drug delivery systems. The area of bioadhesion in drug delivery had started som e 20 years ago by using so-called mucoadhesive polymers. Many of these poly mers were already used as excipients in pharmaceutical formulations. This h as facilitated the development of the first bioadhesive drug products, whic h are now commercially available. A major disadvantage of the hitherto know n mucoadhesives, however, is their non-specificity with respect to the subs trate. In particular for gastro-intestinal applications, this may cause som e premature inactivation and moreover limits the duration of mucoadhesive b onds to the relatively fast mucus turnover. Nevertheless, for some mucoadhe sive polymers other interesting functionalities were discovered, such as th eir ability to modulate epithelial permeability and to inhibit proteolytic enzymes. In contrast to the mucoadhesive polymers, lectins and some other a dhesion molecules specifically recognize receptor-like structures of the ce ll membrane and therefore bind directly to the epithelial cells themselves ("cytoadhesion") rather than to the mucus gel layer. Furthermore, when bioa dhesion is receptor-mediated, it is not only restricted to mere binding, bu t may subsequently trigger the active transport of large molecules or nanos calic drug carrier systems by vesicular transport processes (endo-/ transcy tosis). Rather than only acting as a platform for controlled release system s, the concept of lectin-mediated bioadhesion therefore bears the potential for the controlled delivery of macromolecular biopharmaceuticals at releva nt biological barriers, such as the epithelia of the intestinal or respirat ory tract. (C) 2000 Elsevier Science B.V. All rights reserved.