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

Abstract

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. The present study investigates the biokinetics and clearance of a low single dose (typically 40-400 μg/kg BW) of V-radiolabeled, pure TiO anatase nanoparticles ([V]TiONP) with a median aggregate/agglomerate size of 70 nm in aqueous suspension after intravenous (IV) injection into female Wistar rats. Biokinetics and clearance were followed from one-hour to 4-weeks. The use of radiolabeled nanoparticles allowed a quantitative [V]TiONP balancing of all organs, tissues, carcass and excretions of each rat without having to account for chemical background levels possibly caused by dietary or environmental titanium exposure. Highest [V]TiONP accumulations were found in liver (95.5%ID after one day), followed by spleen (2.5%), carcass (1%), skeleton (0.7%) and blood (0.4%). Detectable nanoparticle levels were found in all other organs. The [V]TiONP content in blood decreased rapidly after 24 h while the distribution in other organs and tissues remained rather constant until day-28. The present biokinetics study is part 1 of a series of studies comparing biokinetics after three classical routes of intake (IV injection (part 1), ingestion (part 2), intratracheal instillation (part 3)) under identical laboratory conditions, in order to test the common hypothesis that IV-injection is a suitable predictor for the biokinetics fate of nanoparticles administered by different routes. This hypothesis is disproved by this series of studies.

Biodistribution, Clearance, and Long‐Term Fate of Clinically Relevant Nanomaterials

“…The biokinetics and biodistribution of nanomaterials following intravenous exposure is different from the biokinetics/biodistribution of nanomaterials administered to the respiratory tract as described earlier . In addition, a very recent series of three publications by Kreyling et al showed that the biokinetics of intravenously injected nanomaterials does not represent a surrogate biokinetic approach for pulmonary or oral routes of exposure . The authors employed 70 nm radiolabeled TiO 2 NPs containing 48 V in rats to study the biokinetics and biodistribution in various tissues over the period of 1 h to 28 d. After intravenous injection, the highest titanium accumulation was found in the liver, followed by the spleen, carcass, skeleton, and blood after 1 h, after which the blood content decreased rapidly, while the distribution in the other organs and tissues remained constant until day 28.…”

Study of223Ra uptake mechanism on hydroxyapatite and titanium dioxide nanoparticles as a function of pH

“…Apart from the previously mentioned reasons, ease of synthesis on a nanoscale size is another argument for selection of these two materials. [2][3][4][5][6][7] Our main area of interest is specically the possibility of the application of the chosen nanomaterials as a drug carrier system for diagnostic, therapeutic or theragnostic radionuclides. The targeting of the nanoparticles to the required tissue can be enabled by two mechanisms.…”

<p>Distribution of SiO₂&nbsp;nanoparticles&nbsp;in 3D liver microtissues</p>

“…17 Hepato-biliary NP clearance turned out to represent a potential excretion route. 18,19 The effect of long-term accumulation in the liver is not clear due to the lack of appropriate investigations. Liver plays a central role in physiological processes in the organism to keep metabolic homeostasis and is the main organ for detoxifying xenobiotics and drugs.…”