Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain

Abstract

Background:Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited.Objectives:We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity.Methods:Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks).Results:The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control.Conclusions:The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure.Citation:Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP234

Intranasal Delivery of Nanoformulations: A Potential Way of Treatment for Neurological Disorders

“…In relation to the CNS, it has been shown that AgNPs, following inhalation and ingestions, cross the BBB and accumulate in the brain [90][91][92]. Patchin et al found rapid translocation of 20 nm AgNPs into the olfactory bulb, with slower and less effective transport of 110 nm silver particles after a 6-h exposure [93]. A study reported very little AgNP absorption (measured as total silver) into the blood after intranasal administration and significantly higher blood concentrations after AgNO3 delivery, and demonstrated that silver found in the blood was due to silver ion release from AgNPs [94].…”

Systems‐level thinking for nanoparticle‐mediated therapeutic delivery to neurological diseases

“…A variety of materials have been utilized for nanoparticle delivery to the brain, including dendrimers, polymers, micelles, hydrogels, liposomes and solid lipids, gold, silica, silver‐based inorganics, iron or iron oxides, quantum dots, and carbon‐based particles . For each of these nanoparticle systems, important physicochemical characteristics that affect drug delivery and efficacy include size, surface charge, composition, molecular weight (MW), material structure, elasticity, shape, and material porosity (Table ).…”

Olfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticles

“…При этом респираторная система рассматривается в качестве одной из основных портальных систем для поступления наноча-стиц в организм. Однако, помимо очевидного воздействия наноаэрозолей на респираторную и сердечнососудистую системы, частицы могут захватываться ольфакторным эпителием носовой полости и проникать в центральную нервную систему (ЦНС) в обход гематоэнцефалического барьера, где способны ускорять развитие нейродегенера-тивных заболеваний (Genter et al, 2012;Heusinkveld et al, 2016;Parmalee, Aschner, 2016;Patchin et al, 2016). Нейро паталогии, возникающие в результате воздействия на организм наноаэрозолей, трудно исследовать вследствие отсроченного характера их возникновения.…”

“…Нейрональный захват (ольфакторные нейроны, нейро-ны тройничного нерва) и их последующий аксональный транссинаптический транспорт в более глубокие струк-туры мозга -наиболее вероятный путь проникновения твердых частиц из носовой полости в мозг (Elder et al, 2006;Genter et al, 2012;Patchin et al, 2016). Участие клеточного транспорта в перемещении твердых частиц из носовой полости в мозг впервые показано на примере нейротропных вирусов.…”