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Age-Dependent Deposition Patterns and Quantitative Biokinetics of Inhaled 20nm Gold Nanoparticles in Rat Lungs
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A1939 - Age-Dependent Deposition Patterns and Quantitative Biokinetics of Inhaled 20nm Gold Nanoparticles in Rat Lungs
Author Block: J. C. Schittny1, W. Moeller2, U. Holzwarth3, S. Hirn2, A. Wenk2, C. Schleh2, M. Schäffler2, N. Haberl2, N. Gibson3, W. G. Kreyling2; 1Inst of Anatomy, Univ of Bern, Bern, Switzerland, 2Institute of Lung Biology and Disease, Helmholtz Center Munich, Neuherberg/Munich, Germany, 3Consumers and Reference Materials, European Commission, Joint Research Centre, Directorate for Health, Ispra, Italy.
Rationale: The increasing use of gold nanoparticles entails an increasing exposure by unintentional inhalation. Therefore, we studied the deposition patterns of inhaled 20-nm gold nanoparticles (AuNPs) in 7-90 days old rats and their biokinetics in adult rats.
Methods: Wistar-Kyoto rats inhaled intratracheally 20-nm 195Au-radiolabeled AuNPs by negative pressure ventilation during two hours. Immediately afterwards lungs were excised and micro-wave dried at 75% of total lung capacity. AuNP deposition was analyzed by SPECT, CT and autoradiography. Quantitative completely balanced biodistributions of all major organs and tissues and total excretion were analyzed 1h-28d after inhalation.
Results: Intratracheal inhalation caused increased AuNP deposition in the caudal lungs independently of age. ~30% AuNP were deposited on airway epithelia for rapid mucociliary clearance. In the broncho-alveolar-lavage (BAL) ~7% AuNP were associated with BAL-cells at any time accounting for 15-20% of the alveolar macrophages (AM). Throughout 28 days >80% of the contemporary AuNP lung burden was not lavageable but relocated into the alveolar epithelium and/or interstitium. Both time-independent fractions suggest re-entrainment back onto the lung epithelium for AM-mediated clearance to the larynx. AuNP clearance from the alveolar region is dominated by long-term-AM-mediated-clearance. In contrast, AuNP-translocation across the air-blood-barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver>soft tissue>spleen>kidneys>skeleton>blood >uterus>heart>brain.
Conclusions: Similar biokinetics data had been found after intratracheal instillation of 18nm AuNP but differed drastically when compared with intravenously injected 18nm AuNP. Same-sized Particle translocation across the rat air-blood-barrier appeared to be reasonably similar to humans.
Author Block: J. C. Schittny1, W. Moeller2, U. Holzwarth3, S. Hirn2, A. Wenk2, C. Schleh2, M. Schäffler2, N. Haberl2, N. Gibson3, W. G. Kreyling2; 1Inst of Anatomy, Univ of Bern, Bern, Switzerland, 2Institute of Lung Biology and Disease, Helmholtz Center Munich, Neuherberg/Munich, Germany, 3Consumers and Reference Materials, European Commission, Joint Research Centre, Directorate for Health, Ispra, Italy.
Rationale: The increasing use of gold nanoparticles entails an increasing exposure by unintentional inhalation. Therefore, we studied the deposition patterns of inhaled 20-nm gold nanoparticles (AuNPs) in 7-90 days old rats and their biokinetics in adult rats.
Methods: Wistar-Kyoto rats inhaled intratracheally 20-nm 195Au-radiolabeled AuNPs by negative pressure ventilation during two hours. Immediately afterwards lungs were excised and micro-wave dried at 75% of total lung capacity. AuNP deposition was analyzed by SPECT, CT and autoradiography. Quantitative completely balanced biodistributions of all major organs and tissues and total excretion were analyzed 1h-28d after inhalation.
Results: Intratracheal inhalation caused increased AuNP deposition in the caudal lungs independently of age. ~30% AuNP were deposited on airway epithelia for rapid mucociliary clearance. In the broncho-alveolar-lavage (BAL) ~7% AuNP were associated with BAL-cells at any time accounting for 15-20% of the alveolar macrophages (AM). Throughout 28 days >80% of the contemporary AuNP lung burden was not lavageable but relocated into the alveolar epithelium and/or interstitium. Both time-independent fractions suggest re-entrainment back onto the lung epithelium for AM-mediated clearance to the larynx. AuNP clearance from the alveolar region is dominated by long-term-AM-mediated-clearance. In contrast, AuNP-translocation across the air-blood-barrier was much smaller leading to persistent retention in secondary organs and tissues in the ranking order liver>soft tissue>spleen>kidneys>skeleton>blood >uterus>heart>brain.
Conclusions: Similar biokinetics data had been found after intratracheal instillation of 18nm AuNP but differed drastically when compared with intravenously injected 18nm AuNP. Same-sized Particle translocation across the rat air-blood-barrier appeared to be reasonably similar to humans.
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