Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration.

Content Provider	Europe PMC
Author	Ernst, Lena M. Mondragón, Laura Ramis, Joana Gustà, Muriel F. Yudina, Tetyana Casals, Eudald Bastús, Neus G. Fernández-Varo, Guillermo Casals, Gregori Jiménez, Wladimiro Puntes, Victor
Editor	Brenneisen, Peter
Copyright Year	2023
Abstract	Nanoparticle (NP) pharmacokinetics significantly differ from traditional small molecule principles. From this emerges the need to create new tools and concepts to harness their full potential and avoid unnecessary risks. Nanoparticle pharmacokinetics strongly depend on size, shape, surface functionalisation, and aggregation state, influencing their biodistribution, accumulation, transformations, and excretion profile, and hence their efficacy and safety. Today, while NP biodistribution and nanoceria biodistribution have been studied often at short times, their long-term accumulation and excretion have rarely been studied. In this work, 3 nm nanoceria at 5.7 mg/kg of body weight was intravenously administrated in a single dose to healthy mice. Biodistribution was measured in the liver, spleen, kidney, lung, brain, lymph nodes, ovary, bone marrow, urine, and faeces at different time points (1, 9, 30, and 100 days). Biodistribution and urinary and faecal excretion were also studied in rats placed in metabolic cages at shorter times. The similarity of results of different NPs in different models is shown as the heterogeneous nanoceria distribution in organs. After the expectable accumulation in the liver and spleen, the concentration of cerium decays exponentially, accounting for about a 50% excretion of cerium from the body in 100 days. Cerium ions, coming from NP dissolution, are most likely excreted via the urinary tract, and ceria nanoparticles accumulated in the liver are most likely excreted via the hepatobiliary route. In addition, nanoceria looks safe and does not damage the target organs. No weight loss or apathy was observed during the course of the experiments.
Journal	Antioxidants (Basel, Switzerland)
Volume Number	12
PubMed Central reference number	PMC10045098
Issue Number	3
PubMed reference number	36979013
e-ISSN	20763921
DOI	10.3390/antiox12030765
Language	English
Publisher	MDPI
Publisher Date	2023-03-21
Access Restriction	Open
Rights License	Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). © 2023 by the authors.
Subject Keyword	nanoparticle biodistribution nanopharmacokinetics nanoceria NP long-term accumulation NP excretion NP dissolution nanosafety
Content Type	Text
Resource Type	Article
Subject	Biochemistry Cell Biology Molecular Biology Physiology Clinical Biochemistry Food Science