Pharmacokinetics of metallic nanoparticles.

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 TiO2 NPs have been developed in rats and the AgNP and TiO2 NP models have been extrapolated to humans to support risk assessment and nanomedicine applications.