Abstract
Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage.
Highlights
As described in various reviews and proof of concept studies gold nanoparticles (AuNPs) present a good strategy for drug and gene delivery as they can deliver a wide variety of cargoes [1,2,3,4]
The question on bioaccumulation of Au when administered as AuNPs for drug delivery purposes has not been extensively investigated and remains unanswered
Bioaccumulation is influenced by the biopersistence of a material which is a result of a biological system’s failure to clear foreign material
Summary
As described in various reviews and proof of concept studies gold nanoparticles (AuNPs) present a good strategy for drug and gene delivery as they can deliver a wide variety of cargoes [1,2,3,4]. Several features of AuNPs make them well suited for drug delivery and the recent advances in the synthesis and characterization techniques of engineered nanomaterials (ENMs) [6]. A paucity of data with regards to the safety of AuNPs. Risk is a function of the product of hazard (a material property), susceptibility of the organism and the exposure. Different models have been used to assess susceptibility [9,10], the bulk of toxicity assessment studies for AuNPs mainly varied the exposure by altering the nanomaterial properties. Nanomaterial properties that can be altered include inter alia; shape, size, surface area, Molecules 2016, 21, 763; doi:10.3390/molecules21060763 www.mdpi.com/journal/molecules
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