Abstract:
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 65Zn 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 65ZnO NPs was biphasic with a rapid initial t1/2 (0.2 - 0.3 hours), and a slower terminal t1/2 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 65ZnO NPs, significantly more 65Zn 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 65Zn from both NPs significantly decreased. However, 65Zn levels in skeletal muscle, skin and blood remained higher from uncoated NPs. Interestingly, 65Zn levels in bone marrow and thoracic lymph nodes were higher from coated 65ZnO NPs. More 65Zn was excreted in the urine from rats instilled with SiO2-coated 65ZnO NPs. After 7 days post-gavage, only 7.4% (uncoated) and 6.7% (coated) of 65Zn dose were measured in all tissues combined. As with instilled NPs, after gavage significantly more 65Zn was measured in skeletal muscle from uncoated NPs and less in thoracic lymph nodes. More 65Zn was excreted in the urine and feces with coated than uncoated 65ZnO 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 65Zn in some extrapulmonary tissues. For both IT instillation and gavage administration, SiO2 coating enhanced transport of 65Zn to thoracic lymph nodes and decreased transport to the skeletal muscle.
journal_name
Part Fibre Toxicoljournal_title
Particle and fibre toxicologyauthors
Konduru NV,Murdaugh KM,Sotiriou GA,Donaghey TC,Demokritou P,Brain JD,Molina RMdoi
10.1186/s12989-014-0044-6subject
Has Abstractpub_date
2014-09-03 00:00:00pages
44issn
1743-8977pii
s12989-014-0044-6journal_volume
11pub_type
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
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journal_title:Particle and fibre toxicology
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
doi:10.1186/1743-8977-8-15
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journal_title:Particle and fibre toxicology
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
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journal_title:Particle and fibre toxicology
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journal_title:Particle and fibre toxicology
pub_type: 评论,信件
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章,评审
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journal_title:Particle and fibre toxicology
pub_type: 杂志文章
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