, 2001 and Matsuo 3-MA ic50 et al., 1997). Depending on the method used for the determination, the thickness of the mucus layer shows marked variation. Fixation of the tissues usually is accompanied by shrinking and lower values are obtained. Endoscopic ultrasound measurements indicate thickness of the mucus in the stomach of 897–1354 μm and in the rectum of 730–1136 μm (Huh et al., 2003) but variation may be quite high because the thickness is dictated by the interplay between
mucus secretion by goblet cells and mucus erosion by mechanical shear and bacterial digestion, particularly in the lower gut (Corfield et al., 1992 and Hoskins and Boulding, 1981). Additionally, pH can vary. The pH of the mucus in the oral cavity is estimated to range around pH 6.6. Gastric mucus shows a wide pH range from 1 to 2 (luminal) to ∼7 (epithelial surface); (Schreiber and Scheid, 1997)). The characteristics facilitating the passage SB431542 through human mucus are relatively well known: electrostatic repulsion from negatively charged sugar moieties favors the penetration of positively charged hydrophilic molecules; the passage of lipophilic compounds is slow (Avdeef and Testa, 2002). It was thought that nanoparticles are incapable to penetrate the mucus layer since recent studies demonstrated that
specific viruses, like the Norwalk virus with a size of 38 nm and human papilloma virus with a size of 55 nm diffused in human mucus as rapidly as they do in water (Olmsted et al., 2001 and Saltzman et al., 1994). The surface of viruses, which are able to permeate the mucus, is densely
coated with positive and negative charges, thus, this net neutral surface charge prevents mucoadhesion (Olmsted et al., 2001). Since the pore size in (cervical) mucus is approximately 100 nm, it is suggested that small particles might also be capable to diffuse through mucus. Olmsted et al. (2001) demonstrated that small viruses diffused unhindered through mucus, whereas polystyrene microspheres in a size of 59 nm and covalently modified with carboxyl-groups, bound more tightly to mucins and bundled them into thick cables. Additional work by Dawson et al. (2003) reported that carboxyl and amine-modified polystyrene particles (100, 200 and 500 nm) Etoposide research buy were embedded in cystic fibrosis sputum. The positively charged particles penetrated more rapidly in the sputum than the negatively charged particles. Furthermore, smaller particles underwent a significantly faster transport. Lai et al. (2007) investigated polystyrene particles in a size range of 100–500 nm. The surfaces of the particles were covalently modified with a high density of low M.W. polyethylene glycol (PEG) and the diffusion in human mucus was studied. The results demonstrated that the neutral surface charge increased the diffusion rate of all particles.