Biodistribution of colloidal gold nanoparticles after intravenous administration: Effect of particle size

Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, Japan.
Colloids and surfaces B: Biointerfaces (Impact Factor: 4.15). 11/2008; 66(2):274-80. DOI: 10.1016/j.colsurfb.2008.07.004
Source: PubMed

ABSTRACT Purpose of the present research work was to evaluate the biological distribution of differently size gold nanoparticles (NP) up on intravenous administration in mice. Another objective was to study effect of particle size on biological distribution of gold NP to enable their diverse applications in nanotechnology. Gold NP of different particle sizes, mainly 15, 50, 100 and 200 nm, were synthesized by modifying citrate ion concentration. Synthesized gold nanoparticles were characterized by SEM and their size distribution was studied by particle size analyzer. Gold NP was suspended in sodium alginate solution (0.5%, w/v) and administered to mice (1g/kg, intravenously) [n=3]. After 24h of administration of gold NP, blood was collected under light ether anesthesia, mice were sacrificed by cervical dislocation and various tissues/organs were removed. The tissues were then washed with saline, homogenized and lysed with aqua regia. The determination of gold in samples was carried out quantitatively by inductively coupled plasma mass spectrometry (ICP-MS). SEM study revealed spherical morphology of gold NP with narrow particle size distribution. Biodistribution study revealed gold NPs of all sizes were mainly accumulated in organs like liver, lung and spleen. The accumulation of gold NP in various tissues was found to be depending on particle size. 15 nm gold NP revealed higher amount of gold and number of particles in all the tissues including blood, liver, lung, spleen, kidney, brain, heart, stomach. Interestingly, 15 and 50 nm gold NP were able to pass blood-brain barrier as evident from gold concentration in brain. Two-hundred nanometers gold NP showed very minute presence in organs including blood, brain, stomach and pancreas. The results revealed that tissue distribution of gold nanoparticles is size-dependent with the smallest 15 nm nanoparticles showing the most widespread organ distribution.

    • "AuNPs and other xenobiotics are taken from the blood circulation system by the mononuclear phagocyte system (MPS) comprising mainly the macrophages of the liver and the spleen [15]. Gold nanoparticles usually are phagocytosed by Kupffer cells of the reticuloendothelial system (RES), and if not broken down by intercellular processes, will remain in this body location for a long time [16]. "
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    ABSTRACT: The gold nanoparticles (AuNP's) exhibit interesting chemical and physical properties and for this reason are intensively tested in medicine. However there is a lack of information about toxicity of those nanoparticles as well as their excretion from the body. Thus, the aim of the present study was to investigate the influence of the route of administration of gold nanoparticles to rats on their distribution in tissues and excretion rate. The experiment was carried out on male Wistar rats. The colloidal gold suspension containing 0.3619mg of particles per milliliter, was administered per 1kg of body weight. Serum levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, glucose and ferric reducing ability of plasma were measured in all investigated animals. It was shown that after oral administration only a small amount of AuNPs was absorbed. In addition, excretion of the metal during consecutive days after po or iv administration was examined. Moreover, the impact of AuNPs on some biochemical parameters 3 days after intravenous administration was studied. It was shown that the AuNPs are mainly cumulated in the liver, lungs and in spleen after iv administration and only slightly removed from the body in urine and feces. Accumulation of those nanoparticles effect in increases of FRAP and glucose level up to 27% and 73%, respectively. This in turn suggests that iv administration of AuNPs may effect in serious medical complications. On the other site, the accumulation in the liver of about 50% of introduced particles to the rats body is promising for phototherapy and it opens "door" for drug transport to this organ. Copyright © 2014. Published by Elsevier Urban & Partner Sp. z o.o.
    Pharmacological reports: PR 06/2015; 67(3). DOI:10.1016/j.pharep.2014.10.019 · 2.17 Impact Factor
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    • ". of De Jong et al. [62] and Sonavane et al. [63]. PEGylated nanoparticles are commonly used to lower cytotoxicity. "
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    ABSTRACT: With the growing interest in the applications of gold nanoparticles in biotechnology and their physiological effects, possible toxicity of gold nanoparticles is becoming an increasingly important issue. A large number of studies carried out over the past few years under a variety of experimental conditions and following different protocols have produced conflicting results, leading to divergent views about the actual safety of gold nanoparticles in human applications. This work is intended to provide an overview of the most recent experimental results and thereby summarize current state-of-the-art. Rather than presenting a comprehensive review of the available literature in this field, which would be impractically broad, we have selected representative examples of both in vivo and in vitro studies, which clearly demonstrate the need for urgent and rigorous standardization of experimental protocols. Despite their significant potential, the safety of gold nanoparticles is highly controversial at this time, and important concerns have been raised that need to be properly addressed. Factors such as shape, size, surface charge, coating, and surface functionalization are expected to influence the interactions of particles with biological systems to a different extent, resulting in different outcomes and influencing the potential of gold nanoparticles for biomedical applications. Moreover, despite continuous attempts to establish a correlation between structure of the particles and their interactions with biological systems, we are still far from elucidating the toxicological profile of gold nanoparticles in an indisputable manner. This review is intended to contribute towards this goal, offering a number of suggestions on how to achieve the systematization of data on the most relevant physico-chemical parameters, which govern and control the toxicity of gold nanoparticles at cellular and whole-organism levels.
    Nano Research 06/2015; 8(6). DOI:10.1007/s12274-014-0697-3 · 6.96 Impact Factor
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    • "(I) Caco-2 cells were treated with increasing concentration of FITC-labelled AHP (AHP- FITC) for 1 h at 37 °C; and (II) Caco-2 cells were treated with 0.1 mM AHP- FITC in the presence of AHP-GNPs for 1 h at either 37 °C (a) or 4 °C (b). Fluorescence intensity was analysed using flow cytometry data corroborate studies reported in the literature that most of the unfunctionalised nanoparticles accumulate mostly in the liver, lungs, kidneys and spleen (Sonavane et al. 2008; Lasagna-Reeves et al. 2010; Wang et al. 2010; Morais et al. 2011). Furthermore, the data showed that AHP-GNPs accumulate preferentially in the WAT, which further substantiate the work in the literature that AHP targets PHB on the WAT vasculature of obese rats in vivo (Kolonin et al. 2004, Hossen et al. 2010, 2012). "
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    ABSTRACT: Obesity is a complex metabolic disease of excessive fat accumulation. It is a worldwide epidemic affecting billions of people. Current pharmacological treatment of obesity remains limited and ineffective due to systemic drug toxicity and undesirable side effects. The current epidemic raises a serious need for development of safer drugs to treat obesity. Nanotechnology-based drug delivery system for administering pharmaceutical compound to achieve therapeutic effects is currently an exciting field in cancer treatment. Drug delivery involves either modification of drug release profile, absorption, distribution and/or elimination, for the benefit of improving drug efficacy and safety. Therefore, nanotechnology holds promise in the treatment of diseases including obesity. Gold nanoparticles (GNPs) functionalised with different biomolecules have been successfully used as drug delivery, labelling and imaging tools in biomedical research. In this study, the binding-specificity and targeting ability of adipose homing peptide (AHP)-functionalised GNPs (AHP-GNPs) were evaluated using flow cytometry and inductively coupled plasma-optical emission spectroscopy. Caco-2 cells and rats fed either chow or a high-fat diet were treated with either unfunctionalised GNPs or AHP-GNPs. Cellular uptake of GNPs was detected in cells treated with AHP-GNPs and not those treated with GNPs alone. Binding of AHP to cells was both temperature- and concentration-dependent. Compared to rats treated with GNPs alone, treatment of obese rats with AHP-GNPs resulted in the targeted delivery of the GNPs to the white adipose tissue (WAT). This paper reports the successful targeting of AHP-functionalised GNPs to WAT of obese rats.
    Journal of Nanoparticle Research 02/2015; 17(2). DOI:10.1007/s11051-015-2904-x · 2.28 Impact Factor
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