Ceria-Engineered Nanomaterial Distribution In, and Clearance From, Blood: Size Matters

Abstract

Aims: Characterize different sized ceria-engineered nanomaterial (ENM) distribution in, and clearance from, blood (compared to the cerium ion) following intravenous infusion. Materials & Methods: Cerium (Ce) was quantified in whole blood, serum and clot (the formed elements) up to 720 h. Results: Traditional pharmacokinetic modeling showed best fit for 5 nm ceria ENM and the cerium ion. Ceria ENMs larger than 5 nm were rapidly cleared from blood. After initially declining, whole blood 15 and 30 nm ceria increased (results that have not been well-described by traditional pharmacokinetic modeling). The cerium ion and 5 and 55 nm ceria did not preferentially distribute into serum or clot, a mixture of cubic and rod shaped ceria was predominantly in the clot, and 15 and 30 nm ceria migrated into the clot over 4 h. Conclusion: Reticuloendothelial organs may not readily recognize five nm ceria. Increased ceria distribution into the clot over time may be due to opsonization. Traditional pharmacokinetic analysis was not very informative. Ceria ENM pharmacokinetics are quite different from the cerium ion.

Keywords::

• blood
• ceria
• distribution in blood
• engineered nanomaterial
• half-life
• pharmacokinetics
• systemic clearance

Financial & competing interests disclosure

The research described in this article has been funded wholly by the US Environmental Protection Agency through STAR Grant RD-833772. It has not been subjected to the Agency‘s required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal studies were approved by the University of Kentucky Institutional Animal Care and Use Committee. The research was conducted in accordance with the Society of Toxicology‘s Guiding Principles in the Use of Animals in Toxicology.

Acknowledgements

The authors gratefully acknowledge RL Florence for her excellent conduct of aspects of this work, and RC MacPhail for his critical and constructive review of a draft of this report.

Additional information

Funding

The research described in this article has been funded wholly by the US Environmental Protection Agency through STAR Grant RD-833772. It has not been subjected to the Agency‘s required peer and policy review and therefore does not necessarily reflect the views of the Agency and no official endorsement should be inferred. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.