Quantitative biokinetics over a 28 day period of freshly generated, pristine, 20 nm silver nanoparticle aerosols in healthy adult rats after a single 1½-hour inhalation exposure.

Background: There is a steadily increasing quantity of silver nanoparticles (AgNP) produced for numerous industrial, medicinal and private purposes, leading to an increased risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure.

Results: To study the fate of inhaled AgNP, healthy adult rats were exposed to 1½-hour intra-tracheal inhalations of pristine Ag-radiolabeled, 20 nm AgNP aerosols (with mean doses across all rats of each exposure group of deposited NP-mass and NP-number being 13.

Quantitative biokinetics over a 28 day period of freshly generated, pristine, 20 nm titanium dioxide nanoparticle aerosols in healthy adult rats after a single two-hour inhalation exposure.

Background: Industrially produced quantities of TiO nanoparticles are steadily rising, leading to an increasing risk of inhalation exposure for both professionals and consumers. Particle inhalation can result in inflammatory and allergic responses, and there are concerns about other negative health effects from either acute or chronic low-dose exposure.

Results: To study the fate of inhaled TiO-NP, adult rats were exposed to 2-h intra-tracheal inhalations of V-radiolabeled, 20 nm TiO-NP aerosols (deposited NP-mass 1.

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

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.

Quantitative biokinetics of titanium dioxide nanoparticles after intratracheal instillation in rats: Part 3.

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and V-radiolabeled [V]TiO nanoparticles has been investigated in healthy adult female Wistar-Kyoto rats at retention time-points of 1 h, 4 h, 24 h, 7 d and 28 d after intratracheal instillation of a single dose of an aqueous [V]TiO-nanoparticle suspension. A completely balanced quantitative biodistribution in all organs and tissues was obtained by applying typical [V]TiO-nanoparticle doses in the range of 40-240 μg·kg bodyweight and making use of the high sensitivity of the radiotracer technique. The [V]TiO-nanoparticle content was corrected for residual blood retained in organs and tissues after exsanguination and for V-ions not bound to TiO-nanoparticles.

Quantitative biokinetics of titanium dioxide nanoparticles after oral application in rats: Part 2.

The biokinetics of a size-selected fraction (70 nm median size) of commercially available and V-radiolabeled [V]TiO nanoparticles has been investigated in female Wistar-Kyoto rats at retention timepoints 1 h, 4 h, 24 h and 7 days after oral application of a single dose of an aqueous [V]TiO-nanoparticle suspension by intra-esophageal instillation. A completely balanced quantitative body clearance and biokinetics in all organs and tissues was obtained by applying typical [V]TiO-nanoparticle doses in the range of 30-80 μg•kg bodyweight, making use of the high sensitivity of the radiotracer technique. The [V]TiO-nanoparticle content was corrected for nanoparticles in the residual blood retained in organs and tissue after exsanguination and for V-ions not bound to TiO-nanoparticles.

Quantitative biokinetics of titanium dioxide nanoparticles after intravenous injection in rats: Part 1.

Submicrometer TiO particles, including nanoparticulate fractions, are used in an increasing variety of consumer products, as food additives and also drug delivery applications are envisaged. Beyond exposure of occupational groups, this entails an exposure risk to the public. However, nanoparticle translocation from the organ of intake and potential accumulation in secondary organs are poorly understood and in many investigations excessive doses are applied.

Biokinetic datasets of PEI F25-LMW complexed and non-complexed P-siRNA within different lung compartments.

Biokinetics data of lung-administered (1 h, 3 h, 8 h), to the P-radioactivity in the whole mouse body. Additionally, data was optimized to the available to the sum of all lung compartments. Methods, other biokinetics data and the discussion of the results are published in "" (Lipka et al.

Biokinetic studies of non-complexed siRNA versus nano-sized PEI F25-LMW/siRNA polyplexes following intratracheal instillation into mice.

Successful gene therapy requires stability and sufficient bioavailability of the applied drug at the site of action. In the case of RNA interference (RNAi), non-viral vectors play a promising role for delivering intact siRNA molecules. We selected a low molecular weight polyethyleneimine (PEI F25-LMW) and investigated the biokinetics of PEI F25-LMW/siRNA polyplexes in comparison to non-complexed siRNA molecules upon intratracheal application into mice.

In vivo integrity of polymer-coated gold nanoparticles.

Inorganic nanoparticles are frequently engineered with an organic surface coating to improve their physicochemical properties, and it is well known that their colloidal properties may change upon internalization by cells. While the stability of such nanoparticles is typically assayed in simple in vitro tests, their stability in a mammalian organism remains unknown. Here, we show that firmly grafted polymer shells around gold nanoparticles may degrade when injected into rats.

Blood protein coating of gold nanoparticles as potential tool for organ targeting.

Nanoparticles (NP) and nanoparticulated drug delivery promise to be the breakthrough for therapy in medicine but raise concerns in terms of nanotoxicity. We present quantitative murine biokinetics assays using polyelectrolyte-multilayer-coated gold NP (AuNP, core diameter 15 and 80 nm; (198)Au radio-labeled). Those were stably conjugated either with human serum albumin (alb-AuNP) or apolipoprotein E (apoE-AuNP), prior to intravenous injection.

Cytotoxic and proinflammatory effects of PVP-coated silver nanoparticles after intratracheal instillation in rats.

Silver nanoparticles (AgNP) are among the most promising nanomaterials, and their usage in medical applications and consumer products is growing rapidly. To evaluate possible adverse health effects, especially to the lungs, the current study focused on the cytotoxic and proinflammatory effects of AgNP after the intratracheal instillation in rats. Monodisperse, PVP-coated AgNP (70 nm) showing little agglomeration in aqueous suspension were instilled intratracheally.

Size dependent translocation and fetal accumulation of gold nanoparticles from maternal blood in the rat.

Background: There is evidence that nanoparticles (NP) cross epithelial and endothelial body barriers. We hypothesized that gold (Au) NP, once in the blood circulation of pregnant rats, will cross the placental barrier during pregnancy size-dependently and accumulate in the fetal organism by 1. transcellular transport across the hemochorial placenta, 2.

Air-blood barrier translocation of tracheally instilled gold nanoparticles inversely depends on particle size.

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 (198)Au-radio-labeled monodisperse, well-characterized, negatively charged AuNP of five different sizes (1.4, 2.

Serum protein identification and quantification of the corona of 5, 15 and 80 nm gold nanoparticles.

When nanoparticles (NP) enter the body they come into contact with body fluids containing proteins which can adsorb to their surface. These proteins may influence the NP interactions with the biological vicinity, eventually determining their biological fate inside the body. Adsorption of the most abundantly binding proteins was studied after an in vitro 24 hr incubation of monodisperse, negatively charged 5, 15 and 80 nm gold spheres (AuNP) in mouse serum by a two-step analysis: proteomic protein identification and quantitative protein biochemistry.

Cellular uptake and localization of inhaled gold nanoparticles in lungs of mice with chronic obstructive pulmonary disease.

Background: Inhalative nanocarriers for local or systemic therapy are promising. Gold nanoparticles (AuNP) have been widely considered as candidate material. Knowledge about their interaction with the lungs is required, foremost their uptake by surface macrophages and epithelial cells.

Effects of silver nanoparticles on the liver and hepatocytes in vitro.

With the increasing use and incorporation of nanoparticles (NPs) into consumer products, screening for potential toxicity is necessary to ensure customer safety. NPs have been shown to translocate to the bloodstream following inhalation and ingestion, and such studies demonstrate that the liver is an important organ for accumulation. Silver (Ag) NPs are highly relevant for human exposure due to their use in food contact materials, dietary supplements, and antibacterial wound treatments.

Biodistribution of inhaled gold nanoparticles in mice and the influence of surfactant protein D.

Background: The pulmonary route is very promising for drug delivery by inhalation. In this regard, nanoparticulate drug delivery systems are discussed, and one very promising nano carrier example is gold nanoparticles (Au NP). Directly after their deposition, inhaled Au NP come into contact with pulmonary surfactant protein D (SP-D).

Efficient internalization and intracellular translocation of inhaled gold nanoparticles in rat alveolar macrophages.

Aim: To investigate the relationship of alveolar macrophages and inhaled nanoparticles (NPs) in the lung.

Materials & Methods: Rats were exposed by inhalation to 16-nm gold NPs for 6 h, and ultramicroscopic observation on the frequency and localization of gold NPs within lavaged macrophages was performed for 7 days.

Results & Discussion: The majority of macrophages examined on day 0 (94%) contained internalized gold NPs, and the percentage decreased to 59% on day 7.

Binding of polystyrene and carbon black nanoparticles to blood serum proteins.

Context: Once inhaled, nanoparticles (NP) deposit on the lung surface and have first contact with the epithelial lung lining fluid (ELF) rich in proteins, which may bind to NP.

Objective: In this study, we investigate the parameters that influence the binding between NP and proteins.

Materials And Methods: We used the proteins albumin, transferrin (TF), and apolipoprotein A-1 (all known as proteins from ELF) and different NP (polystyrene NP with negative, positive, and neutral surface coatings, Printex G and Printex 90) as models.

Size and surface charge of gold nanoparticles determine absorption across intestinal barriers and accumulation in secondary target organs after oral administration.

It is of urgent need to identify the exact physico-chemical characteristics which allow maximum uptake and accumulation in secondary target organs of nanoparticulate drug delivery systems after oral ingestion. We administered radiolabelled gold nanoparticles in different sizes (1.4-200 nm) with negative surface charge and 2.

Particle size-dependent and surface charge-dependent biodistribution of gold nanoparticles after intravenous administration.

Gold nanoparticles (GNP) provide many opportunities in imaging, diagnostics, and therapies of nanomedicine. Hence, their biokinetics in the body are prerequisites for specific tailoring of nanomedicinal applications and for a comprehensive risk assessment. We administered (198)Au-radio-labelled monodisperse, negatively charged GNP of five different sizes (1.

Biodistribution of PEG-modified gold nanoparticles following intratracheal instillation and intravenous injection.

Besides toxicity tests, biokinetic studies are a fundamental part of investigations to evaluate a safe and sustainable use of nanoparticles. Today, gold nanoparticles (Au NPs) are known to be a versatile tool in different areas such as science, engineering or medicine. In this study, we investigated the biokinetics after intravenous and intratracheal applications of poly(ethylene glycol) (PEG) modified Au NPs compared to plain Au NPs.

Size dependence of the translocation of inhaled iridium and carbon nanoparticle aggregates from the lung of rats to the blood and secondary target organs.

Currently, translocation of inhaled insoluble nanoparticles (NP) across membranes like the air-blood barrier into secondary target organs (STOs) is debated. Of key interest are the involved biological mechanisms and NP parameters that determine the efficiency of translocation. We performed NP inhalation studies with rats to derive quantitative biodistribution data on the translocation of NP from lungs to blood circulation and STOs.

Efficient elimination of inhaled nanoparticles from the alveolar region: evidence for interstitial uptake and subsequent reentrainment onto airways epithelium.

Background: There is ongoing discussion that inhaled nanoparticles (NPs, < 100 nm) may translocate from epithelial deposition sites of the lungs to systemic circulation.

Objectives And Methods: We studied the disappearance of NPs from the epithelium by sequential lung retention and clearance and bronchoalveolar lavage (BAL) measurements in healthy adult Wistar Kyoto (WKY) rats at various times over 6 months after administration of a single 60- to 100-min intratracheal inhalation of iridium-192 ((192)Ir)-radiolabeled NPs. A complete (192)Ir balance of all organs, tissues, excretion, remaining carcass, and BAL was performed at each time point.