Bioavailability, distribution and clearance of tracheally-instilled and gavaged uncoated or silica-coated zinc oxide nanoparticles

Background: Nanoparticle pharmacokinetics and biological effects are influenced by several factors. We assessed the effects of amorphous SiO2 coating on the pharmacokinetics of zinc oxide nanoparticles (ZnO NPs) following intratracheal (IT) instillation and gavage in rats. Methods: Uncoated and SiO2-coated ZnO NPs were neutron-activated and IT-instilled at 1 mg/kg or gavaged at 5 mg/kg. Rats were followed over 28 days post-IT, and over 7 days post-gavage. Tissue samples were analyzed for Zn-65 radioactivity. Pulmonary responses to instilled NPs were also evaluated at 24 hours. Results: SiO2-coated ZnO elicited significantly higher inflammatory responses than uncoated NPs. Pulmonary clearance of both (ZnO)-Zn-65 NPs was biphasic with a rapid initial t(1/2) (0.2 - 0.3 hours), and a slower terminal t(1/2) of 1.2 days (SiO2-coated ZnO) and 1.7 days (ZnO). Both NPs were almost completely cleared by day 7 (>98%). With IT-instilled (ZnO)-Zn-65 NPs, significantly more Zn-65 was found in skeletal muscle, liver, skin, kidneys, cecum and blood on day 2 in uncoated than SiO2-coated NPs. By 28 days, extrapulmonary levels of Zn-65 from both NPs significantly decreased. However, Zn-65 levels in skeletal muscle, skin and blood remained higher from uncoated NPs. Interestingly, Zn-65 levels in bone marrow and thoracic lymph nodes were higher from coated (ZnO)-Zn-65 NPs. More Zn-65 was excreted in the urine from rats instilled with SiO2-coated (ZnO)-Zn-65 NPs. After 7 days post-gavage, only 7.4% (uncoated) and 6.7% (coated) of Zn-65 dose were measured in all tissues combined. As with instilled NPs, after gavage significantly more Zn-65 was measured in skeletal muscle from uncoated NPs and less in thoracic lymph nodes. More Zn-65 was excreted in the urine and feces with coated than uncoated (ZnO)-Zn-65 NPs. However, over 95% of the total dose of both NPs was eliminated in the feces by day 7. Conclusions: Although SiO2-coated ZnO NPs were more inflammogenic, the overall lung clearance rate was not affected. However, SiO2 coating altered the tissue distribution of Zn-65 in some extrapulmonary tissues. For both IT instillation and gavage administration, SiO2 coating enhanced transport of Zn-65 to thoracic lymph nodes and decreased transport to the skeletal muscle.