Technical report 122

Translocation is determined by solubility and size

A biokinetic study was designed (Kreyling et al, 2002), in order to study particle translocation from the lung to secondary organs using radiolabelled iridium (192Ir) in soluble and insoluble forms with the following administration techniques:

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Administered UF 192Ir via systemic circulation, gavage, or to the lungs have very low solubility and no uptake from the GI tract; particles passed the gut and were excreted via the faeces. The administered soluble 192Ir indicated that, when found in soluble form (administered to the lung), it is excreted mostly through the urine with negligible organ uptake, suggesting that insoluble form of particles is required for extra pulmonary translocation.

Smaller particles (15-nm vs. 80-nm) showed greater uptake to the interstitial spaces. A very small fraction of 192Ir particles deposited in the lower respiratory tract translocated from the lungs into liver, spleen, heart, brain and the carcass. Only the liver showed a time-dependent pattern. Due to the fact that, systemic injection of 192Ir resulted in fractions found in similar organs, the plausible pathway suggested was transport from lung epithelium into the pulmonary vasculature and then into systemic circulation. Translocation was larger for 15-nm particles, which showed higher interstitial uptake than larger particles, by a factor of 5-10. The rate of systemic translocation of insoluble UF 192Ir was rather small but shown to be size dependent, suggesting an inverse particle-size-dependent transport phenomenon into blood circulation.

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