, 1991). These effects are known to influence

oral bioavailability of conventional drugs but are even more important for the effects of NMs because NMs readily adsorb proteins (Cedervall et al., 2007 and Lynch et al., 2009), which on the one hand, determines biological actions and, on the other, influence the dispersion of nanoparticles. Carboxyl polystyrene particles, for instance show a high tendency of aggregation, when suspended in FBS-containing medium (Mayer et al., 2009 and Xia et al., 2006). For other NMs like carbon nanotubes, protein has a dispersing effect (Bihari et al., 2008, Heister et al., 2010 and Sager et al., 2007). Permeation through the gastrointestinal barrier has been shown for micro- and nanoparticles. The absorption is estimated to be about 15–250 times higher for nanoparticles BTK inhibitor (Desai et al., 1996). These barriers consist of cellular (epithelium) and acellular parts (dead cells, mucus). For the entire tract, composed of the oral cavity, the esophagus, the stomach and the intestine, mucus represents an efficient acellular barrier. Mucus consists of mucin proteins (highly glycosylated extracellular GDC 0449 proteins with characteristic gel-forming properties), antiseptic proteins (lysozyme) and other proteins (lactoferrin), inorganic salts and water. The major functions

are the protection and the lubrication of the underlying tissue. The saliva, which is produced by the salivary glands, mainly consists of water (up to 99.5%), inorganic

salts, proteins, and mucins. The high molecular weight mucin MG1 can bind to the surface Branched chain aminotransferase of the epithelium and build the so-called mucus layer, displaying the acellular barrier of the oral cavity (Bykov, 1996 and Bykov, 1997). The thickness of this mucus layer is different before and after swallowing and measures between 70 and 100 μm (Collins and Dawes, 1987, Harris and Robinson, 1992 and Lagerlof and Dawes, 1984). It displays a thick gelatinous like layer, structured as a 3-dimensional network with high water-holding capacity. It is highly viscoelastic and displays a shear thinning gel acting as lubricant. It protects the epithelial cell layers from pathogens, toxins and particles and enables the exchange of nutrients, water and gases (Knowles and Boucher, 2002). Once substances are swallowed they pass the esophagus. Esophageal glands, which are located throughout the esophagus, secrete mucus directly onto the surface (Squier and Kremer, 2001). Additionally, exocrine glands in the submucosa produce a secretion with high bicarbonate concentration. This is necessary to neutralize refluxing stomach acid (Long and Orlando, 1999). The mucus of the following parts, stomach and small and large intestine, is mainly produced by intraepithelial cells. In the first part of the small intestine (duodenum) also exocrine glands in the submucosa are located. The thickness of the mucus layer shows high variations depending on the localization in the gastrointestinal tract.