AUTHOR=Heckman Karin L. , Estevez Ana Y. , DeCoteau William , Vangellow Stephanie , Ribeiro Samantha , Chiarenzelli Joseph , Hays-Erlichman Bonnie , Erlichman Joseph S. 

TITLE=Variable in Vivo and in Vitro Biological Effects of Cerium Oxide Nanoparticle Formulations

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01599

DOI=10.3389/fphar.2019.01599

ISSN=1663-9812

ABSTRACT=<p>Cerium oxide nanoparticles (CeNPs) exhibit redox capacity <italic>in vitro</italic> with efficacy in <italic>in vivo</italic> disease models of oxidative stress. Here we compare, in parallel, three CeNP formulations with distinct chemical stabilizers and size. <italic>In vitro</italic> assays revealed antioxidant activity from all the CeNPs, but when administered to mice with a reactive oxygen species (ROS) mediated model of multiple sclerosis, only custom-synthesized Cerion NRx (CNRx) citrate-EDTA stabilized CeNPs provided protection against disease. Detectable levels of ceria and reduced ROS levels in the brains of CNRx CeNP-treated mice imply that these CeNPs' unique properties influence tissue distribution and subsequent biological activity, suggesting why differing CeNP formulations yield different <italic>in vivo</italic> effects in various models. Further, the variation in <italic>in vivo</italic> vs <italic>in vitro</italic> results with these CeNP formulations highlights the necessity for <italic>in vivo</italic> studies that confirm whether the inherent catalytic activity of CeNPs is maintained after transport and distribution within intact biological systems.</p>