Toxicity, biodistribution and oxidative damage caused by zirconia nanoparticles after intravenous injection

Background: As a promising nanomaterial for biomedical applications, zirconia nanoparticles (ZrO₂) have aroused concern recently, but the toxicity of ZrO₂ in vivo has received little attention. Purpose: The aim of this study is to demonstrate the systematic single dose toxicity, biodistribution and oxidative damage of ZrO₂ in vivo after intravenous injection in mice. Materials and methods: Ten ICR mice were used at the high dose of ZrO₂ including 600, 500, 400 and 300mg/kg. Maximum tolerated dose (MTD) of 150 nm ZrO₂ was determined as 500mg/kg. Hematology analysis and blood biochemical assay were determined for the evaluation of oxidative damage caused by ZrO₂. Biodistribution of ZrO₂ was investigated by ICP-OES and TEM. Results: Mice treated with higher dose (500mg/kg) showed significant spread in white blood cell counts (p<0.05). Especially, the serum ALT levels of 500mg/kg groups increased significantly (p<0.05) compared with the control group. ZrO₂ particles would not induce any changes in appearance and micromorphology of liver at 100 and 350mg/kg. Spleen samples showed no significant changes in micromorphology of the lymphoid follicles and in the size of the red pulp after injection of ZrO₂ at all doses. The serum of ZrO₂-treated animals (350 and 500mg/kg) has reduced levels of SOD compared to the control group (p<0.05). ZrO₂ persists in membrane-enclosed vesicles called lysosomes in the liver and spleen macrophages without abnormal changes of ultrastructure. Conclusion: These findings would contribute to the future development of ZrO₂-based drug delivery system and other biomedical applications.