Lectin-mediated drug delivery: The second generation of bioadhesives

被引:213
作者
Lehr, CM [1 ]
机构
[1] Univ Saarland, Dept Biopharmaceut & Pharmaceut Technol, D-66123 Saarbrucken, Germany
关键词
mucoadhesion; endocytosis; atomic force microscopy; confocal laser scanning microscopy; intestinal and alveolar epithelial cells;
D O I
10.1016/S0168-3659(99)00228-X
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:19 / 29
页数:11
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