Air–Blood Barrier Translocation of Tracheally Instilled Gold Nanoparticles Inversely Depends on Particle Size

Abstract

Gold nanoparticles (AuNP) provide many opportunities in imaging, diagnostics, and therapy in nanomedicine. For the assessment of AuNP biokinetics, we intratracheally instilled into rats a suite of 198Au-radio-labelled monodisperse, well-characterized, negatively-charged AuNP of five different sizes (1.4, 2.8, 5, 18, 80, 200 nm) and 2.8 nm AuNP with positive surface charges. At 1-h, 3-h, and 24-h the biodistribution of the AuNP was quantitatively measured by gamma-spectrometry to be used for comprehensive risk assessment. Our study shows, as AuNP get smaller, they are more likely to cross the air-blood-barrier (ABB) depending strongly on the inverse diameter d−1 of their gold core; i.e. their specific surface area (SSA). So, 1.4 nm AuNP (highest SSA) translocated most while 80 nm AuNP (lowest SSA) translocated least, but 200 nm particles did not follow the d−1 relation translocating significantly higher than 80 nm AuNP. However, relative to the AuNP which had crossed the ABB, their retention in most of the secondary organs and tissues was SSA-independent. Only renal filtration, retention in blood and excretion via urine further declined with d−1 of AuNP core. Translocation of 5, 18 and 80 nm AuNP is virtually complete after 1-h, while 1.4 nm AuNP continue to translocate until 3-h. Translocation of negatively charged 2.8 nm AuNP was significantly higher than for positively charged 2.8 nm AuNP. Our study shows that translocation across the ABB and accumulation and retention in secondary organs and tissues are two distinct processes, both depending specifically on particle characteristics such as SSA and surface charge.

Lung inflammation does not affect the clearance kinetics of lipid nanocapsules following pulmonary administration

“…In the lung, the nanocapsules remained primarily in the lung lining fluid avoiding phagocytosis by alveolar macrophages, a behaviour which was attributed to the pegylated ('stealth') surface chemistry and the small particle size, which reduce macrophage detection and phagocytosis [36][37][38], whilst promoting translocation across the air-blood barrier [29,30,39]. The increase in signal in the liver at t=24 h post-administration (absent in the 111 In-DTPA groups) suggests that at least a fraction of the lung dose was able to cross the air-blood barrier and enter into the systemic circulation as intact nanoparticles, accumulating subsequently in the liver [29,30]. Previous studies have shown that lipid nanocapsules are highly stable in biological fluids, such as cell culture media and gastric fluids [40,41]; although nanocapsule stability and drug release studies have yet to be performed in lung lining fluid or lung lining fluid mimetics.…”

“…4E), which may indicate that animals with lung inflammation had a lower inspiratory capacity and did not aspirate liquid into the lungs to the same extent as their healthy counterparts. Notably, only 111 In-LNC50-treated animals showed an accumulation of signal in the liver, peaking at t = 24 h, possibly indicating that a portion of the nanocapsule dose were able to traverse the air-blood barrier and enter the systemic circulation intact, whereby they encountered circulating phagocytic cells in the blood and were cleared to the liver [29,30]. The lung clearance kinetics of 111 In-DTPA and 111 In-LNC50 suspensions were calculated from the imaging data after normalisation to the original lung dose.…”

Revisiting the classification of NIR-absorbing/emitting nanomaterials for in vivo bioapplications

“…Internalized NPs are then transported and deposited at systemic sites, including the brain and bones. 230 Applications of NIR materials for imaging and cancer eradication often rely on systemic injections directly into circulation or into tissues. Data on the distribution and clearance of different types of NPs are still insufficient, but some conclusions may be helpful for the design of new nanomaterials for biomedical purposes.…”

Comparative modeling of exposure to airborne nanoparticles released by consumer spray products

“…Moreover, the barrier separating gas phase and blood in the alveoli consists of surfactant and only a few cells. Transition into the bloodstream is therefore conceivable and has already been shown for various materials (Balasubramanian et al, 2013;Kendall & Holgate, 2012;Kreyling et al, 2014). In contrast, dermal penetration is considered negligible at least for healthy skin (Labouta & Schneider, 2013;Nohynek & Dufour, 2012), and oral intake of some nanoscale materials is already commonplace (Peters et al, 2012;Weir et al, 2012).…”