Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration
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 functiona...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-03-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/12/3/765 |
| _version_ | 1797613790068473856 |
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| author | Lena M. Ernst Laura Mondragón Joana Ramis Muriel F. Gustà Tetyana Yudina Eudald Casals Neus G. Bastús Guillermo Fernández-Varo Gregori Casals Wladimiro Jiménez Victor Puntes |
| author_facet | Lena M. Ernst Laura Mondragón Joana Ramis Muriel F. Gustà Tetyana Yudina Eudald Casals Neus G. Bastús Guillermo Fernández-Varo Gregori Casals Wladimiro Jiménez Victor Puntes |
| author_sort | Lena M. Ernst |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T06:59:37Z |
| format | Article |
| id | doaj.art-7dd6ac6461cf496f97acc0d66699be14 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T06:59:37Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-7dd6ac6461cf496f97acc0d66699be142023-11-17T09:19:27ZengMDPI AGAntioxidants2076-39212023-03-0112376510.3390/antiox12030765Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose AdministrationLena M. Ernst0Laura Mondragón1Joana Ramis2Muriel F. Gustà3Tetyana Yudina4Eudald Casals5Neus G. Bastús6Guillermo Fernández-Varo7Gregori Casals8Wladimiro Jiménez9Victor Puntes10Vall d’Hebron Research Institute (VHIR), 08035 Barcelona, SpainVall d’Hebron Research Institute (VHIR), 08035 Barcelona, SpainVall d’Hebron Research Institute (VHIR), 08035 Barcelona, SpainInstitut Català de Nanociència I Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, 08193 Barcelona, SpainInstitut Català de Nanociència I Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, 08193 Barcelona, SpainVall d’Hebron Research Institute (VHIR), 08035 Barcelona, SpainInstitut Català de Nanociència I Nanotecnologia (ICN2), CSIC, The Barcelona Institute of Science and Technology (BIST), Campus UAB, Bellaterra, 08193 Barcelona, SpainService of Biochemistry and Molecular Genetics, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainService of Biochemistry and Molecular Genetics, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainService of Biochemistry and Molecular Genetics, Hospital Clinic, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, SpainVall d’Hebron Research Institute (VHIR), 08035 Barcelona, SpainNanoparticle (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.https://www.mdpi.com/2076-3921/12/3/765nanoparticle biodistributionnanopharmacokineticsnanoceriaNP long-term accumulationNP excretionNP dissolution |
| spellingShingle | Lena M. Ernst Laura Mondragón Joana Ramis Muriel F. Gustà Tetyana Yudina Eudald Casals Neus G. Bastús Guillermo Fernández-Varo Gregori Casals Wladimiro Jiménez Victor Puntes Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration Antioxidants nanoparticle biodistribution nanopharmacokinetics nanoceria NP long-term accumulation NP excretion NP dissolution |
| title | Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration |
| title_full | Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration |
| title_fullStr | Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration |
| title_full_unstemmed | Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration |
| title_short | Exploring the Long-Term Tissue Accumulation and Excretion of 3 nm Cerium Oxide Nanoparticles after Single Dose Administration |
| title_sort | exploring the long term tissue accumulation and excretion of 3 nm cerium oxide nanoparticles after single dose administration |
| topic | nanoparticle biodistribution nanopharmacokinetics nanoceria NP long-term accumulation NP excretion NP dissolution |
| url | https://www.mdpi.com/2076-3921/12/3/765 |
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