Tight junctions paracellular absorption

Keywords Nasal absorption Air-interfaced culture Absorption enhancer Liquid-covered culture Mucociliary clearance Nasal epithelial cell mono-layer Paracellular absorption Tight junction Transcelluar absorption Drug transport... 

Anderberg, E. K. Lindmark, T. Artursson, P., Sodium caprate ehcits dilations in human intestinal tight junctions and enhances drug absorption by the paracellular route, Pharm. Res. 10, 857-864 (1993). 

The paracellular pathway, between the epithelial cells, is both size- (MW, volume) and charge-dependent [60, 109, 110]. In general, compounds that are limited to paracellular transport are not efficiently absorbed due to the small available absorptive area and the restriction by tight junctions. The molecular weight cut-off seems to be around 400 g mol-1 and 300 g mol-1 for the small and large intestine respectively, and 300 g mol-1 for the Caco-2 cell monolayers [60], which shows the more colonic nature of the Caco-2 monolayer model. Compounds with a... 

Another drawback is the lack of correlation for paracellularly transported compounds. For example, some low molecular weight hydrophilic compounds (e.g., ranitidine, atenolol, furosemide, and metformin) showed poor permeability in the Caco-2 model despite an absorption larger than 50% in humans [168], This is due to the smaller size of the paracellular channels (controlled by tight junctions) in the Caco-2 model compared to human small intestine [146],... 

It is often mentioned that when drugs are absorbed paracellularly, they are dragged by a local water flux through the tight junctions. In this context, it is interesting to mention the Pappenheimer hypothesis [169,175,176], which suggests that the absorption of solutes across... 

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