Age-Dependent Rat Lung Deposition Patterns of Inhaled 20 Nanometer Gold Nanoparticles and their Quantitative Biokinetics in Adult Rats

Abstract

The increasing use of gold nanoparticles leads to a possible increase of exposure by inhalation. Therefore, we have studied the deposition patterns of inhaled 20 nm gold nanoparticles (AuNP) in 7-90 day old rats and their biokinetics in 60 day old ones. Wistar-Kyoto rats inhaled intratracheally 20 nm Au-radiolabeled AuNP by negative pressure ventilation over 2 h. Immediately afterward lungs were excised, inflated and microwave dried. AuNP deposition was analyzed by single-photon emission computed tomography, computed-tomography and autoradiography. Completely balanced, quantitative biodistributions in major organs and all body tissues and total excretion were analyzed from 1 h to 28 d after inhalation. Intratracheal inhalation caused AuNP deposition predominately in the caudal lungs, independent of age. About 30% AuNP were deposited on airway epithelia and rapidly cleared by mucociliary clearance. About 80% of AuNP deposited in alveoli was relocated from the epithelium into the interstitium within 24 h and was inaccessible to broncho-alveolar lavage. During interstitial long-term retention, re-entrainment within macrophages back onto the lung epithelium and to the larynx and gastrointestinal tract (GIT) dominated AuNP clearance (rate 0.03 d) 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 issue > spleen > kidneys > skeleton > blood > uterus > heart > brain. The age-independent, inhomogeneous AuNP deposition was probably caused by the negative pressure ventilation. Long-term AuNP clearance was dominated by macrophage-mediated transport from the interstitium to the larynx and GIT. Translocation across the rat air-blood barrier appeared to be similar to that of humans for similar sized AuNP.

How high resolution 3-dimensional imaging changes our understanding of postnatal lung development

“…Furthermore, structural details obtained at high resolution in 3D are very important for our understanding of ventilation and particle deposition. E.g., they are important for simulations of acinar airflow and particle deposition (Sznitman et al 2010 ; Henry et al 2012 ; Tsuda et al 2008 ; Hofemeier et al 2018 ) or for the correlation between the amount of the deposition of inhaled particles in rat lungs and the size of the airspaces (Semmler-Behnke et al 2012 ; Kreyling et al 2018 ). Therefore, the application of modern cutting edge imaging and quantitative histological techniques advanced our anatomical and physiological knowledge significantly.…”

Three-Dimensional Quantitative Co-Mapping of Pulmonary Morphology and Nanoparticle Distribution with Cellular Resolution in Nondissected Murine Lungs

“…Moreover, existence of NPs in the esophagus indicated that NPs can be cleared within a few minutes towards the digestive tract by either mucociliary clearance or coughing ( Figure 3d and Video S6). 38 Quantitative analysis of dose and regional deposition of inhaled MF It became evident that each lung had a different autofluorescence level due to differences in the optical properties of the lungs, in lung volume, and LSFM instrument uncertainties (despite the same settings of LSFM were used for all lungs). Here, the average of measured total fluorescence intensity from blank lungs was (11.1 ± 3.33) ×10 10 and the relative high standard deviation of 30.2% demonstrates the variations in tissue-induced fluorescence due to lung and instrument variations.…”

Which Nanobasics Should Be Taught in Medical Schools?

“…[56][57][58][59][60] For example, the occurrence of side effects may be delayed, given that some nanotechnology platforms, such as nanogold, can accumulate in tissues and persist longer than traditional medicines. 61 As a result, some side effects might not be captured during the trial itself or even during the first few years of postapproval long-term safety monitoring. Although clinical trials are often powered to detect strong early negative safety signals, years of experience with medications is required before clinicians can fully understand the long-term effects of exposure.…”