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 some 20 years ago by using so-called mucoadhesive polymers. Many of these polymers were already used as excipients in pharmaceutical formulations. This has facilitated the development of the first bioadhesive drug products, which are now commercially available. A major disadvantage of the hitherto known mucoadhesives, however, is their non-specificity with respect to the substrate. In particular for gastro-intestinal applications, this may cause some premature inactivation and moreover limits the duration of mucoadhesive bonds to the relatively fast mucus turnover. Nevertheless, for some mucoadhesive polymers other interesting functionalities were discovered, such as their ability to modulate epithelial permeability and to inhibit proteolytic enzymes. In contrast to the mucoadhesive polymers, lectins and some other adhesion molecules specifically recognize receptor-like structures of the cell membrane and therefore bind directly to the epithelial cells themselves ("cytoadhesion") rather than to the mucus gel layer. Furthermore, when bioadhesion is receptor-mediated, it is not only restricted to mere binding, but may subsequently trigger the active transport of large molecules or nanoscalic drug carrier systems by vesicular transport processes (endo-/transcytosis). Rather than only acting as a platform for controlled release systems, the concept of lectin-mediated bioadhesion therefore bears the potential for the controlled delivery of macromolecular biopharmaceuticals at relevant biological barriers, such as the epithelia of the intestinal or respiratory tract.
Lehr
C M
CM
Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Im Stadtwald, Bldg. 8.1, 66123, Saarbrücken, Germany. lehr@rz.uni-sb.de
D000269:Adhesives; D001672:Biocompatible Materials; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002460:Cell Line; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D037102:Lectins; D008081:Liposomes; D018613:Microscopy, Confocal; D008863:Microspheres; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D014909:Wheat Germ Agglutinins
D000269:Adhesives; D001672:Biocompatible Materials; D004337:Drug Carriers; D005456:Fluorescent Dyes; D037102:Lectins; D008081:Liposomes; D014909:Wheat Germ Agglutinins