In 333 BC, while wintering at Gordium in Asia Minor, Alexander the Great opened the door to the East by cutting the 'Gordian knot'. Opening the door to the development of efficient and cost effective nano-delivery systems, from an industrial point of view, for macromolecular drugs necessitates the solution of another 'Gordian knot' problem, namely, that of enhanced permeation of nanoparticles through the mucus gel barrier. Apart from oral mucosal vaccinations where Peyer's patches, which are not coated by a mucus gel layer, are targeted, the development of mucosal nanoparticulate delivery systems for macromolecular drugs such as therapeutic peptides, oligo- and polysaccharides and DNA-based drugs only makes sense, if effective strategies are available to overcome the mucus gel barrier. Similarly to Alexander the Great, who simply cut the 'Gordian knot' into parts, the mucus gel layer barrier, consisting of mucus glycoproteins that are highly entangled and knotted, will have to be 'cut' by 'chemical swords' such as mucolytic agents in order to open the door to mucosally administered macromolecular drugs for systemic circulation. According to these considerations it is the mission of the large EU-project ALEXANDER to develop nano-delivery systems to overcome the various mucus gel barriers without destroying them. Based on results gained within this project fundamental knowledge how to overcome the mucus gel barrier in a highly efficient manner shall be provided leading to more potent mucosal drug delivery systems in general.
|The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 280761|