Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration.
Lena M ErnstLaura MondragónJoana RamisMuriel F GustàTetyana YudinaEudald CasalsNeus G BastúsGuillermo Fernández-VaroGregori CasalsWladimiro JiménezVictor PuntesPublished in: Antioxidants (Basel, Switzerland) (2023)
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.
Keyphrases
- oxide nanoparticles
- pet imaging
- body weight
- small molecule
- bone marrow
- lymph node
- weight loss
- urinary tract
- bariatric surgery
- photodynamic therapy
- protein protein
- solid state
- human health
- mesenchymal stem cells
- risk assessment
- quantum dots
- computed tomography
- white matter
- roux en y gastric bypass
- sentinel lymph node
- oxidative stress
- blood brain barrier
- brain injury
- obese patients