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 (CaCO₃) is widely used as a dietary supplement; however, oral absorption efficiency of CaCO₃ is extremely low, which may be overcome by applying nano-sized materials. In this study, we evaluated the efficacy of food grade nano CaCO₃ in comparison with that of bulk- or reagent grade nano CaCO₃ in terms of cytotoxicity, cellular uptake, intestinal transport, and oral absorption. Cytotoxicity results demonstrated that nano-sized CaCO₃ particles were slightly more toxic than bulk materials in terms of oxidative stress and membrane damage. Cellular uptake behaviors of CaCO₃ nanoparticles were different from bulk CaCO₃ or Ca2+ ions in human intestinal epithelial cells, showing efficient cellular internalization and elevated intracellular Ca2+ levels. Meanwhile, CaCO₃ nanoparticles were efficiently transported by microfold (M) cells in vitro model of human intestinal follicle-associated epithelium, in a similar manner as Ca2+ ions did. Biokinetic study revealed that the biological fate of CaCO₃ particles was different from Ca2+ 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.
Keywords: calcium carbonate; cellular uptake; cytotoxicity; intestinal transport; oral absorption.