Biodistribution and long-term fate of silver nanoparticles functionalized with bovine serum albumin in rats

Garza-Ocañas, Lourdes; Ferrer, Domingo; Burt, Justin L.; Dı́az-Torres, L.A.; Cabrera, Mónica Ramírez; Rodríguez, Víctor; Rangel, Rubén Luján; Romanovicz, Dwight K.; José–Yacamán, Miguel

doi:10.1039/b916107d

Cited by 80 publications

(70 citation statements)

References 24 publications

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“…For particles below or above the defined size range it must be expected that the TKs are different than described by our model, which is supported by several in vivo studies that used silver particle sizes below 15 nm 50,66,93 and above 150 nm. 68 As mentioned above, good results were obtained with a size-independent uptake of nanosilver via the capillaries of the organs, whereas a size-dependent particle uptake had to be implemented for the MPS compartments of the lung, liver, and spleen.…”

Section: Distribution and Excretionmentioning

confidence: 63%

“…In studies where the nanosilver was intravenously administered, the fraction of silver that could be recovered from the organs and fecal and urine excretion is usually in the range of less than 1% to 55%. 26,68,93 On the contrary, after injecting intravenously 1 and 10 mg/kg of 7.9 nm silver NPs, Park et al 66 recovered 180% and 700% of silver, respectively, from the liver alone. The authors did not discuss reasons for these high recoveries.…”

Section: Distribution and Excretionmentioning

confidence: 99%

“…66,67,93,95 Studies with polystyrene and iron oxide NPs showed that the bone marrow plays an important role in the clearance of NPs. [43][44][45] Therefore, for our nanosilver PBPK models we assumed that NPs are cleared from the blood by the bone marrow.…”

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confidence: 99%

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A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Bachler

Goetz

Konrad³

2013

IJN

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Silver is a strong antibiotic that is increasingly incorporated into consumer products as a bulk, salt, or nanosilver, thus potentially causing side-effects related to human exposure. However, the fate and behavior of (nano)silver in the human body is presently not well understood. In order to aggregate the existing experimental information, a physiologically based pharmacokinetic model (PBPK) was developed in this study for ionic silver and nanosilver. The structure of the model was established on the basis of toxicokinetic data from intravenous studies. The number of calibrated parameters was minimized in order to enhance the predictive capability of the model. We validated the model structure for both silver forms by reproducing exposure conditions (dermal, oral, and inhalation) of in vivo experiments and comparing simulated and experimentally assessed organ concentrations. Therefore, the percutaneous, intestinal, or pulmonary absorption fraction was estimated based on the blood silver concentration of the respective experimental data set. In all of the cases examined, the model could successfully predict the biodistribution of ionic silver and 15-150 nm silver nanoparticles, which were not coated with substances designed to prolong the circulatory time (eg, polyethylene glycol). Furthermore, the results of our model indicate that: (1) within the application domain of our model, the particle size and coating had a minor influence on the biodistribution; (2) in vivo, it is more likely that silver nanoparticles are directly stored as insoluble salt particles than dissolve into Ag + ; and (3) compartments of the mononuclear phagocytic system play a minor role in exposure levels that are relevant for human consumers. We also give an example of how the model can be used in exposure and risk assessments based on five different exposure scenarios, namely dietary intake, use of three separate consumer products, and occupational exposure.

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Section: Distribution and Excretionmentioning

confidence: 63%

Section: Distribution and Excretionmentioning

confidence: 99%

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A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Bachler

Goetz

Konrad³

2013

IJN

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“…Signs of silver-induced brain damage were observed; however, EM did not reveal silver-ENMs in the brain. 40 It is possible that the silver-ENMs associated with the BBB and released silver ions to produce the toxicity, rather than being an effect of silver-ENMs. A previous study using the in situ brain perfusion method reported that polymer-based nanoparticles entered the central nervous system within 60 seconds, without influencing BBB integrity.…”

Section: Discussionmentioning

confidence: 99%

Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial

Mo¹,

Tseng²,

Wu³

et al. 2012

IJN

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Purpose: Ceria engineered nanomaterials (ENMs) have current commercial applications and both neuroprotective and toxic effects. Our hypothesis is that ceria ENMs can associate with brain capillary cells and/or cross the blood-brain barrier. Methods: An aqueous dispersion of ∼5 nm ceria ENM was synthesized and characterized in house. Its uptake space in the Sprague Dawley rat brain was determined using the in situ brain perfusion technique at 15 and 20 mL/minute flow rates; 30, 100, and 500 µg/mL ceria perfused for 120 seconds at 20 mL/minute; and 30 µg/mL perfused for 20, 60, and 120 seconds at 20 mL/ minute. The capillary depletion method and light and electron microscopy were used to determine its capillary cell and brain parenchymal association and localization. Results: The vascular space was not significantly affected by brain perfusion flow rate or ENM, demonstrating that this ceria ENM did not influence blood-brain barrier integrity. Cerium concentrations, determined by inductively coupled plasma mass spectrometry, were significantly higher in the choroid plexus than in eight brain regions in the 100 and 500 µg/mL ceria perfusion groups. Ceria uptake into the eight brain regions was similar after 120-second perfusion of 30, 100, and 500 µg ceria/mL. Ceria uptake space significantly increased in the eight brain regions and choroid plexus after 60 versus 20 seconds, and it was similar after 60 and 120 seconds. The capillary depletion method showed 99.4% ± 1.1% of the ceria ENM associated with the capillary fraction. Electron microscopy showed the ceria ENM located on the endothelial cell luminal surface. Conclusion: Ceria ENM association with brain capillary endothelial cells saturated between 20 and 60 seconds and ceria ENM brain uptake was not diffusion-mediated. During the 120-second ceria ENM perfusion, ceria ENM predominately associated with the surface of the brain capillary cells, providing the opportunity for its cell uptake or redistribution back into circulating blood.

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“…Relatively little data especially with respect to long-term exposures are available concerning biodistribution and toxicokinetics (Aggarwal et al 2009;Estevanato et al 2012;Menjoge et al 2010;Garza-Ocanas et al 2010;Katsnelson et al 2011). Meanwhile, some general principles have been convincingly demonstrated.…”

Section: Biodistribution Toxicokinetics and Accumulationmentioning

confidence: 99%

The nanotoxicology revolution

2013

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Biodistribution and long-term fate of silver nanoparticles functionalized with bovine serum albumin in rats

Cited by 80 publications

References 24 publications

A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

A physiologically based pharmacokinetic model for ionic silver and silver nanoparticles

Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial

The nanotoxicology revolution

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