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        In Vitro Systems for Studying Epithelial Transport of Macromolecules

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        Biological barriers, typically, represented by epithelial tissues are the main hindrance against uncontrolled uptake of a variety of substances. However, the delivery across a biological barrier is a crucial factor in the development of drugs. As the permeability of macromolecular drugs is very limited, new delivery strategies have to be developed and further improved. Thereby, nanoparticle carriers offer an enormous potential for the controlled delivery of active substances into the organism. Besides an intensive study for the reason of risk assessment and toxicology, the possible transport enhancement caused by nanoparticles must be quantified. A powerful tool for these studies is in vitro cell culture models imitating the more complex in vivo situation under controlled conditions. We use polyethylenimine as model enhancer mimicking toxicological effects and altered barrier function in the epithelial in vitro model, Calu-3. Cytotoxicity assays based on different mechanisms and transport properties of a low-permeability marker with and without delivery enhancer are described.
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