Lectins for gastrointestinal targeting - 15 years on

In the mid-1980s, the concept of bioadhesion using synthetic polymers emerg ed, and brought with it the promise of improved efficiency for the delivery of drugs via mucosal surfaces. Studies in the author's laboratory concentr ated on 'biological' bioadhesion using the naturally-occurring proteins, le ctins, which recognise and bind sugars in glycoconjugates, such as those fo und on the surfaces of cells. Tomato Lectin (TL) was extensively studied as a putative non-toxic lectin with potential for drug targeting/delivery to the gastrointestinal (GI) tract. In vitro, the TL displayed impressive bind ing to the intestinal mucosa, but in vivo failed to significantly modify in testinal transit. A number of research groups have coupled the TL to microp articles, and significant systemic uptake of these has been observed in ani mal studies. Polymers with pendant sugars have also been shown to be bioadh esive, by interacting with endogenous lectins present on the cells of the G I tract. The use of lectins to target to Peyer's patches and diseased tissu es in the colon is an interesting development, but much work remains to be done. Lectins also have potential in mucosal vaccines. Before advanced drug delivery systems using lectins can be realised, rigorous evaluation of the ir toxicity and immunogenicity will be required, but they clearly offer a n umber of possibilities for GI drug targeting systems in the future.