Brain‐targeted distribution and high retention of silver by chronic intranasal instillation of silver nanoparticles and ions in Sprague–Dawley rats

Abstract

The wide applications of silver nanoparticles (AgNPs) have been concerned regarding their unintentional toxicities. Different exposure modes may cause distinct accumulation, retention and elimination profiles, which are closely related with their toxicities. Unlike silver accumulation profiles through other regular administration modes, the biodistribution, accumulation and elimination of AgNPs by intranasal instillation are not fully understood. This study conducted intranasal instillation of polyvinylpyrrolidone-coated AgNPs in neonatal Sprague-Dawley rats at doses of 1 and 0.1 mg kg À1 day À1 for 4 and 12 weeks, respectively. The 4-week recovery was also designed after the 12-week exposure. Silver concentrations in the main tissues or organs were periodically monitored. Parallel exposures using silver ion were performed for the comparative studies. No physiological alterations were observed in AgNP exposures. In comparison, 1 mg kg À1 day À1 silver ions decreased body weight gain and caused mortality of 18.2%, showing ionic silver had a relatively higher toxicity than AgNPs. A relatively higher silver accumulation was observed in silver ion groups than AgNP groups. The silver ion release could not fully explain silver accumulation in AgNP exposures, showing silver distribution caused by particulate silver occurred in vivo. The highest silver concentration was in the liver at week 4, while it shifted to the brain after a 12-week exposure. Dose-related silver accumulation occurred for both AgNP and silver ion groups. The time course revealed a uniquely high concentration and retention of brain silver, implying chronic intranasal instillation caused brain-targeted silver accumulation. These findings provided substantial evidence on the potential neuronal threat from the intranasal administration of AgNPs or silver colloid-based products.

Intranasal Chromium Induces Acute Brain and Lung Injuries in Rats: Assessment of Different Potential Hazardous Effects of Environmental and Occupational Exposure to Chromium and Introduction of a Novel Pharmacological and Toxicological Animal Model

“…In correspondence, many studies showed that absorption of substances through intranasal cavity provides them a direct delivery to the brain through both the olfactory and trigeminal nerves [16]. In agreement, other research groups reported a brain-targeted distribution of manganese [25] and silver [26] following intranasal instillation.…”

Involvement of Programmed Cell Death in Neurotoxicity of Metallic Nanoparticles: Recent Advances and Future Perspectives

“…The concentrations of TiO 2 NPs in the brain, liver, spleen, kidneys, lungs, and heart were elevated after the rats were exposed to NPs through single or repeated intravenous injection [8]. When the rats were exposed to silver NPs through chronic intranasal instillation, the brain subunits including the cortex, hippocampus, cerebellum, olfactory bulb, and medulla exhibited higher contents of NPs [9]. The exposure to silver NPs through single intravenous injection can also increase the NP levels in the mouse brain [25, 26].…”

“…[7]. In addition, several in vivo studies have demonstrated that once animals are exposed to metallic NPs through intravenous injection [8], intranasal instillation [9], oral administration [10], inhalation [11], and intraperitoneal injection [12], NPs can be absorbed into the body and then re-distributed into secondary organs, such as the brain, liver, spleen, lungs, and kidneys. The brain is an important organ susceptible to harmful substances [13–15], and impairment to the brain is irreversible.…”

Silver nanoparticles: Electron transfer, reactive oxygen species, oxidative stress, beneficial and toxicological effects. Mini review

“…Numerous in vivo studies have revealed that AgNPs, administered through intravenous injection, oral administration (van der Zande et al, ), intranasal instillation (Wen et al, ) and intraperitoneal injection (Daniel, Tharmaraj, Sironmani, & Pitchumani, ) can be absorbed and detected in many organs including, kidney, liver, lungs, spleen and brain (Song et al, ; Tang et al, ). Once located in the organs they generate ROS, which leads to cellular dysfunction via OS (Anna et al, 2015; AshaRani et al, ; Braydich‐Stolle et al, ; Choi et al, ; Gonzales, Lison, & Kirsch‐Volders, ; Guo et al, ; Guo et al, ; Han et al, ; Heidary, Ghasemi, Zijoud, & Ranjbar, ; Hussain, Hess, Gearhart, & Schlager, ; Kim et al, ; Lee et al, ; Patlolla, Hacckett, & Tchounwou, ; Song et al, ).…”

“…Numerous in vivo studies have revealed that AgNPs, administered through intravenous injection, oral administration (van der Zande et al, 2012), intranasal instillation (Wen et al, 2016) and…”