Titanium dioxide (TiO
2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO
2 NPs have increased. In order to comprehend their in vivo behavior and
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Titanium dioxide (TiO
2) nanoparticles (NPs) have been widely applied in various industrial fields, such as electronics, packaging, food, and cosmetics. Accordingly, concerns about the potential toxicity of TiO
2 NPs have increased. In order to comprehend their in vivo behavior and potential toxicity, we must evaluate the interactions between TiO
2 NPs and biomolecules, which can alter the physicochemical properties and the fate of NPs under physiological conditions. In the present study, in vivo solubility, oral absorption, tissue distribution, and excretion kinetics of food grade TiO
2 (f-TiO
2) NPs were evaluated following a single-dose oral administration to rats and were compared to those of general grade TiO
2 (g-TiO
2) NPs. The effect of the interactions between the TiO
2 NPs and biomolecules, such as glucose and albumin, on oral absorption was also investigated, with the aim of determining the surface interactions between them. The intestinal transport pathway was also assessed using 3-dimensional culture systems. The results demonstrate that slightly higher oral absorption of f-TiO
2 NPs compared to g-TiO
2 NPs could be related to their intestinal transport mechanism by microfold (M) cells, however, most of the NPs were eliminated through the feces. Moreover, the biokinetics of f-TiO
2 NPs was highly dependent on their interaction with biomolecules, and the dispersibility was affected by modified surface chemistry.
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