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

Abstract

BackgroundNanoparticle 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.MethodsUncoated 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.ResultsSiO2-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.ConclusionsAlthough 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.

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

“…As an example, amorphous silica seems to dissolve in tissues over time . Additionally, dissolution of ZnO NMs might be important for their rapid distribution from the lung (Konduru et al 2014) and slow uptake on the skin (Osmond-McLeod et al 2014). Cadmium-based QDs and Ag are examples of NMs that are likely to be oxidised in physiological environments ).…”

“…Finally, the faecal excretion in the gavaged rats was higher than in IT instilled rats. For both IT instillation and gavage administration, SiO 2 coating enhanced transport of Zn to thoracic lymph nodes and decreased transport to the skeletal muscle, leading the authors to conclude that coating of NMs may alter the tissue distribution of Zn NMs in some extra-pulmonary tissues (Konduru et al 2014).…”

“…Endocytosis can occur by receptor-mediated mechanisms, pinocytosis and clathrin-mediated mechanisms, and by formation of caveolae. Finally, it is thought that macrophages play a key role in redistribution of NMs in the lung by transporting material to the thoracic lymph nodes (Konduru et al 2014, Zhao et al 2011. Cell transformation and tissue remodelling are probably also important in long-term distribution of NMs in the lung.…”

Biological Reactivity of Zinc Oxide Nanoparticles With Mammalian Test Systems: an Overview

“…Even though increased levels of Zn 2+ were found to be associated with in vivo tissues, the source of these ions (ZnO NPs or ZnCl 2 ) did not seem to influence their biodistribution after intraperitoneal injection [82]. Konduru and coworkers demonstrated that upon intratracheal instillation of 65 ZnO NPs in rats, the clearance of 65 Zn was rapid, with only 16-18% of the dose remaining after 2 days, 1.9% after a week and almost none by the end of the 28-day study period [83]. Similarly, inhalation of ZnO NP leads to an increase in Zn 2+ ions in the BALF of exposed animals, although this increase was not long lasting and the Zn levels returned to basal levels within few weeks [72].…”

Toxicological implications of released particulate matter during thermal decomposition of nano-enabled thermoplastics

“…Nano-enabled thermoplastics or nanocomposites can contain nanofillers such as silica nanoparticles (Stojanović et al , 2013), clays (Fang et al , 2008), metal oxides (Perkgoz et al , 2011), carbon fibers (Al-Saleh et al , 2013) and carbon nanotubes (Sahoo et al , 2010) enabling extensive mechanical and electrical properties. Although, ENMs afford many useful properties, certain ENMs can cause adverse health effects such as cytotoxicity (DeLoid et al , 2016; DeLoid et al , 2014; Pirela et al , 2013; Pirela et al , 2014a), genotoxicity (Watson et al , 2013), epigenetic changes (Lu et al , 2016a; Lu et al , 2016b), and lung inflammation upon exposure (Borm et al , 2006; Konduru et al , 2014; Pirela, et al, 2013; Pirela et al , 2016). With this in mind, considerable concern over the hazards that may ensue due to the release of ENMs during consumer use and disposal of nano-enabled thermoplastics has created efforts to understand potential exposures across the life cycle of nano-enabled products (Bouillard et al , 2013; Grassian et al , 2016; Pirela et al , 2014b; Sisler et al , 2014; Wohlleben et al , 2011; Wohlleben and Neubauer, 2016).…”