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Mucus is tenacious. It sticks to most particles, preventing their penetration to the
epithelial surface. Multiple low-affinity hydrophobic interactions play a major role
in these adhesive interactions. Mucus gel is also shear-thinning, making it an excellent
lubricant that ensures an unstirred layer of mucus remains adherent to the epithelial
surface. Thus nanoparticles (NP) must diffuse readily through the unstirred adherent
layer if they are to contact epithelial cells efficiently. This article reviews some
of the physiological and biochemical properties that form the mucus barrier. Capsid
viruses can diffuse through mucus as rapidly as through water and thereby penetrate
to the epithelium even though they have to diffuse 'upstream' through mucus that is
being continuously secreted. These viruses are smaller than the mucus mesh spacing,
and have surfaces that do not stick to mucus. They form a useful model for developing
NP for mucosal drug delivery.