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As discussed, physical barriers, like skin and mucus, are the first line of defense for the immune system. Clearly, the importance of the mucus barrier to health and disease is extremely well documented. However, the criteria that govern transport through the mucus barrier and the mechanism by which mucus helps prevent viruses from infecting mucosal surface are largely unknown. Mucus will stick to most particles, making it difficult to penetrate to the epithelial surface. It is also shear-thinning, so an unstirred layer of mucus remains adherent to the epithelial surface. Mucus has evolved to have robust barrier mechanisms that can trap and immobilize pathogens, nanoparticles, etc. before they contact epithelial surfaces. Many naturally occurring substances can easily bypass the mucus layer (capsid viruses, ethanol, salts, etc.). These viruses are smaller than the mucus mesh spacing and do not stick to the mucus, therefore they are a useful model to mimic. There are various barriers that must be overcome, which has lead to many potential approaches for developing nanoparticles that overcome the mucus barrier. One study, conducted by chemical engineers at Johns Hopkins University in 2008, engineered the first drug-delivery particles capable of passing through the human mucus barrier. This feat opened the doors to treating a wide range of diseases ranging from lung and cervical cancer to cystic fibrosis. Their technique involved improving the coatings of the drug, which would allow for faster penetration for a wide array of particle sizes. They ultimately coated the nanoparticles with an inexpensive polymer material, which allowed nanoparticles to pass through mucus linings and lead to more targeted drug delivery, including improve... ... middle of paper ... ... are accessible to topical delivery. A recent study conducted at the University of Austin tested topically applied particulate systems, both micro and nano, for their potential to interact with mucus and influence the diffusion of model drugs across the mucus barrier. Functionalized polystyrene and diesel particulate matter were topically applied to mucus models, then assessed and compared to controls for drug permeation rates. On average, permeation rate of drugs increased 2-fold following topical application. Particle physiochemical properties indicated significant interactions occurred between mucus and the particles as determined by zeta potential charges and size changes. This research shows that topically applied particles interacting with the mucus barrier can cause a significant disruption, which would allow for improved drug delivery and enhanced exposure.

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