Skin, mucosal and blood-brain barrier kinetics of model cyclic depsipeptides : the mycotoxins beauvericin and enniatins

This research takes off by giving an introduction to the wonderful world of the chemically very diverse cyclic depsipeptides (CDPs). This family of compounds is biosynthetically produced by an extreme variety of natural organisms, such as bacteria and fungi, which can be found all over the world. CDPs exhibit multiple biological activities, serving as interesting drug leads for the development of medicines. For the first time a classification system for CDPs was introduced. Some CDPs synthesised by fungi, however, can also be toxic and are potentially harmful. In scientific literature, there is a lack of a clear definition for these so-called mycotoxins, although very important for risk analyses. Therefore, we presented a new, quantitative expressed U+2018mycotoxinU+2019 definition, by means of the philosophical concept of explication. Recently, beauvericin and enniatins are recognised as U+2018emergingU+2019 mycotoxins. Exposure to these CDPs should not be considered as trivial, given their potential biological effects and presence as food and feed contaminants. Subsequent to the successful development of a bioanalytical method for the determination of beauvericin and enniatins in diverse matrices, their kinetic transport across the skin, oral mucosal and blood-brain barrier was quantitatively evaluated. Finally, a pharmaceutical preparation, containing enniatins as active ingredient and used in the treatment of upper respiratory tract infections, was investigated. Because of the negative risk-benefit ratio, we questioned its use in these innocent respiratory infections. For the same reason, the European Medicines Agency (EMA) has very recently endorsed the recall of these medicines from the European market.

ISBN:9789461974372

Publication year:2016

Accessibility:Open