Cytotoxicity, Uptake Behaviors, and Oral Absorption of Food Grade Calcium Carbonate Nanomaterials

Calcium is the most abundant mineral in human body and essential for the formation and maintenance of bones and teeth as well as diverse cellular functions. Calcium carbonate (CaCO(3)) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO(3) is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO(3) in comparison with that of bulk- or reagent grade nano CaCO(3) in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO(3) particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO(3) nanoparticles were different from bulk CaCO(3) or Ca(2+) ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca(2+) levels. Meanwhile, CaCO(3) nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca(2+) ions did. Biokinetic study revealed that the biological fate of CaCO(3) particles was different from Ca(2+) ions; however, in vivo, its oral absorption was not significantly affected by particle size. These findings provide crucial information to understand and predict potential toxicity and oral absorption efficiency of food grade nanoparticles.