The properties of the mucus barrier, a unique gel--how can nanoparticles cross it?

The key criterion for a nanoparticle drug-delivery system is the ability to produce substantial bioavailability without damaging the physiological protective mechanisms. The main area for drug delivery is the aerodigestive tract. All epithelial surfaces have a membrane-bound layer and in the lung this layer is surmounted by a gel layer. In the gastrointestinal tract the membrane-bound mucin layer is covered by a mucus bilayer. The pore sizes of mucus gels are around 100 to 200 nm. Consequently, only nanoparticles in this size range could potentially penetrate without modification of these layers. To study nanoparticle permeation with results that pertain to in vivo conditions, native mucus mucin preparations must be used. Strategies to increase pores in mucus gels are discussed herein.