Food Additive Solvents Increase the Dispersion, Solubility, and Cytotoxicity of ZnO Nanoparticles

Zinc oxide (ZnO) nanoparticles (NPs) are utilized as a zinc (Zn) fortifier in processed foods where diverse food additives can be present. Among them, additive solvents may strongly interact with ZnO NPs by changing the dispersion stability in food matrices, which may affect physico-chemical and dissolution properties as well as the cytotoxicity of ZnO NPs. In this study, ZnO NP interactions with representative additive solvents (methanol, glycerin, and propylene glycol) were investigated by measuring the hydrodynamic diameters, solubility, and crystallinity of ZnO NPs. The effects of these interactions on cytotoxicity, cellular uptake, and intestinal transport were also evaluated in human intestinal cells and using in vitro human intestinal transport models. The results revealed that the hydrodynamic diameters of ZnO NPs in glycerin or propylene glycol, but not in methanol, were significantly reduced, which is probably related to their high dispersion and increased solubility under these conditions. These interactions also caused high cell proliferation inhibition, membrane damage, reactive oxygen (ROS) generation, cellular uptake, and intestinal transport. However, the crystal structure of ZnO NPs was not affected by the presence of additive solvents. These findings suggest that the interactions between ZnO NPs and additive solvents could increase the dispersion and solubility of ZnO NPs, consequently leading to small hydrodynamic diameters and different biological responses.