Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies
In recent animal experiments with suspensions of radiolabeled TiO2 nanoparticles large and highly variable radioactivity fractions were retained in disposable plastic syringes. After unloading between 10% and up to 70% of the loaded dose were still present in the syringes. As a consequence the effec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01293/full |
| _version_ | 1818844755280265216 |
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| author | Uwe Holzwarth Unai Cossío Jordi Llop Jordi Llop Wolfgang G. Kreyling |
| author_facet | Uwe Holzwarth Unai Cossío Jordi Llop Jordi Llop Wolfgang G. Kreyling |
| author_sort | Uwe Holzwarth |
| collection | DOAJ |
| description | In recent animal experiments with suspensions of radiolabeled TiO2 nanoparticles large and highly variable radioactivity fractions were retained in disposable plastic syringes. After unloading between 10% and up to 70% of the loaded dose were still present in the syringes. As a consequence the effectively delivered nanoparticle dose to the animals was frequently much smaller than the nominal dose of the nanoparticles loaded into the syringe. The high variability of this nanoparticle retention challenges the application of a precise, predefined dose and creates a major error source when normalizing organ and tissue contents to the dose loaded into the syringe, which is usually set as the applied dose. A control study was performed employing six commonly used syringe types with seven types of radiolabeled oxide and metallic nanoparticles. For this purpose the syringes were loaded with a given volume of nanoparticle suspension, the radioactivity was measured, the syringe was unloaded and the activity measurement was repeated with the empty syringe. The highest retention values were found when using TiO2 nanoparticle suspensions with Tuberkulin type syringes. In the worst case between 6.6% and 79.1% of the nanoparticles were retained in the syringe. When using the same nanoparticle suspension with an insulin-type syringe the retention was reduced to 1.4% to 20.6%. For amorphous silica nanoparticles the maximum observed retention was 8% and for Au nanoparticles it was 5.1%. Further data gathered from in vivo animal imaging studies show that nanoparticle retention in syringes also affects experiments with nanoparticles such as exosomes, polymersomes, and protein-based nanoparticles investigated for possible applications in nanomedicine. Since the retention is highly variable the effectively applied dose cannot be determined by applying a simple syringe retention factor. The present work shall alert to the problem and illustrate its possible magnitude and unpredictable variability. As mitigation strategy adequate checks with different syringe types are proposed in order to find out whether a given combination of syringe type and nanoparticle suspension is affected by nanoparticle retention and, if necessary, to select a different syringe type that minimizes retention. |
| first_indexed | 2024-12-19T05:18:48Z |
| format | Article |
| id | doaj.art-851de270db3143448b90fe04f1a4b83d |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-19T05:18:48Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-851de270db3143448b90fe04f1a4b83d2022-12-21T20:34:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-11-011010.3389/fphar.2019.01293486220Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology StudiesUwe Holzwarth0Unai Cossío1Jordi Llop2Jordi Llop3Wolfgang G. Kreyling4Joint Research Centre (JRC), European Commission, Ispra, ItalyRadiochemistry and Nuclear Imaging, CIC biomaGUNE, San Sebastian, SpainRadiochemistry and Nuclear Imaging, CIC biomaGUNE, San Sebastian, SpainCentro de Investigación Biomédica en Red, Enfermedades Respiratorias–CIBERES Parque Tecnológico de San Sebastián, San Sebastián, SpainInstitute of Epidemiology, and Institute of Lung Biology and Disease, Helmholtz Zentrum München–German Research Center for Environmental Health, Munich, GermanyIn recent animal experiments with suspensions of radiolabeled TiO2 nanoparticles large and highly variable radioactivity fractions were retained in disposable plastic syringes. After unloading between 10% and up to 70% of the loaded dose were still present in the syringes. As a consequence the effectively delivered nanoparticle dose to the animals was frequently much smaller than the nominal dose of the nanoparticles loaded into the syringe. The high variability of this nanoparticle retention challenges the application of a precise, predefined dose and creates a major error source when normalizing organ and tissue contents to the dose loaded into the syringe, which is usually set as the applied dose. A control study was performed employing six commonly used syringe types with seven types of radiolabeled oxide and metallic nanoparticles. For this purpose the syringes were loaded with a given volume of nanoparticle suspension, the radioactivity was measured, the syringe was unloaded and the activity measurement was repeated with the empty syringe. The highest retention values were found when using TiO2 nanoparticle suspensions with Tuberkulin type syringes. In the worst case between 6.6% and 79.1% of the nanoparticles were retained in the syringe. When using the same nanoparticle suspension with an insulin-type syringe the retention was reduced to 1.4% to 20.6%. For amorphous silica nanoparticles the maximum observed retention was 8% and for Au nanoparticles it was 5.1%. Further data gathered from in vivo animal imaging studies show that nanoparticle retention in syringes also affects experiments with nanoparticles such as exosomes, polymersomes, and protein-based nanoparticles investigated for possible applications in nanomedicine. Since the retention is highly variable the effectively applied dose cannot be determined by applying a simple syringe retention factor. The present work shall alert to the problem and illustrate its possible magnitude and unpredictable variability. As mitigation strategy adequate checks with different syringe types are proposed in order to find out whether a given combination of syringe type and nanoparticle suspension is affected by nanoparticle retention and, if necessary, to select a different syringe type that minimizes retention.https://www.frontiersin.org/article/10.3389/fphar.2019.01293/fullnanoparticle retention in plastic syringesdisposable plastic syringesdosage uncertaintydosage reproducibilityin vivo studiesnanomedicine |
| spellingShingle | Uwe Holzwarth Unai Cossío Jordi Llop Jordi Llop Wolfgang G. Kreyling Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies Frontiers in Pharmacology nanoparticle retention in plastic syringes disposable plastic syringes dosage uncertainty dosage reproducibility in vivo studies nanomedicine |
| title | Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies |
| title_full | Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies |
| title_fullStr | Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies |
| title_full_unstemmed | Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies |
| title_short | Unpredictable Nanoparticle Retention in Commonly Used Plastic Syringes Introduces Dosage Uncertainties That May Compromise the Accuracy of Nanomedicine and Nanotoxicology Studies |
| title_sort | unpredictable nanoparticle retention in commonly used plastic syringes introduces dosage uncertainties that may compromise the accuracy of nanomedicine and nanotoxicology studies |
| topic | nanoparticle retention in plastic syringes disposable plastic syringes dosage uncertainty dosage reproducibility in vivo studies nanomedicine |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01293/full |
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