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WIREs Nanomed Nanobiotechnol
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Pharmacokinetics of metallic nanoparticles

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Metallic nanoparticles (NPs) have been widely applied in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. This review focuses on gold and silver (Ag) NPs, and briefly discusses iron oxide, titanium dioxide (TiO2), and zinc oxide NPs. Pharmacokinetics of metallic NPs depends on the particle type, size, surface charge, surface coating, protein binding, exposure route, dose, and species. Generally, blood half‐life is shorter in rodents than in larger laboratory animals (e.g., rabbits or monkeys) and differs between intravenous and oral exposures. Oral, dermal, or inhalational absorption is low (≤5%), but may increase with smaller sizes, negative charge, and appropriate coatings. Metallic NPs can be distributed throughout the body, primarily accumulating in the liver, spleen, and lymph node due to nonspecific uptake by reticuloendothelial cells, and could remain in the body for ≥6 months. Metallic NPs (≤100 nm) can cross the blood–brain barrier (BBB), favored by coating with BBB‐permeable neuropeptides. Placental transfer depends on the stage of embryonic/placental maturation and surface composition, and may be enhanced by coating with biocompatible molecules (e.g., ferritin or polyethylene glycol). Renal and biliary excretion is generally low due to persistent accumulation in tissues, but renal elimination could be substantially increased with smaller sizes and specific coatings (e.g., glutathione). Physiologically based pharmacokinetic models for gold/dendrimer composite nanodevices, AgNPs, and TiO2NPs have been developed in rats and the AgNP and TiO2NP models have been extrapolated to humans to support risk assessment and nanomedicine applications. WIREs Nanomed Nanobiotechnol 2015, 7:189–217. doi: 10.1002/wnan.1304 This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Number of publications on the pharmacokinetics or biodistribution of gold, silver (a), iron oxide, titanium dioxide, and zinc oxide (b) nanoparticles (NPs). Data for 2014 are limited to May 31.
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Perfused tissue pharmacokinetic model. This simple pharmacokinetic model can be used to describe distribution of metallic nanoparticles (NPs) from the arterial to venous vasculature, as detailed in our earlier study. (Model structure was adapted from Ref .)
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Proposed metabolism pathways of silver nanoparticles (AgNPs) in the body after oral exposure. These metabolic processes are mainly based on Ref .
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Proposed physiologically based pharmacokinetic (PBPK) model structure for metallic nanoparticles (NPs). RES represents reticuloendothelial system (RES). (Modified based on Refs 27, 62, 94, and 95.)
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