scholarly journals Pharmacokinetics, Biodistribution, and Biosafety of PEGylated Gold Nanoparticles In Vivo

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1702
Author(s):  
Katarina Kozics ◽  
Monika Sramkova ◽  
Kristina Kopecka ◽  
Patricia Begerova ◽  
Alena Manova ◽  
...  

Despite the obvious advantages of gold nanoparticles for biomedical applications, controversial and incomplete toxicological data hamper their widespread use. Here, we present the results from an in vivo toxicity study using gold nanoparticles coated with polyethylene glycol (PEG-AuNPs). The pharmacokinetics and biodistribution of PEG-AuNPs were examined in the rat’s liver, lung, spleen, and kidney after a single i.v. injection (0.7 mg/kg) at different time intervals. PEG-AuNPs had a relatively long blood circulation time and accumulated primarily in the liver and spleen, where they remained for up to 28 days after administration. Increased cytoplasmic vacuolation in hepatocytes 24 h and 7 days after PEG-AuNPs exposure and apoptotic-like cells in white splenic pulp 24 h after administration has been detected, however, 28 days post-exposure were no longer observed. In contrast, at this time point, we identified significant changes in lipid metabolism, altered levels of liver injury markers, and elevated monocyte count, but without marked biological relevance. In blood cells, no DNA damage was present in any of the studied time intervals, with the exception of DNA breakage transiently detected in primary kidney cells 4 h post-injection. Our results indicate that the tissue accumulation of PEG-AuNPs might result in late toxic effects.

Nanoscale ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 1256-1264 ◽  
Author(s):  
Rafaela García-Álvarez ◽  
Marilena Hadjidemetriou ◽  
Ana Sánchez-Iglesias ◽  
Luis M. Liz-Marzán ◽  
Kostas Kostarelos

A detailed study is presented of in vivo protein corona formation on anisotropic gold nanoparticles, after blood circulation in mice.


Author(s):  
Le Wang ◽  
Sixiang Li ◽  
Leni Zhong ◽  
Qizhen Li ◽  
Shaoqin Liu ◽  
...  

The pharmacokinetics is a critical factor determining the clinical applicability of nanomaterials. Systematic study of the pharmacokinetics of functional nanomaterials is thus significant for promoting their applications. Herein, we take...


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Cemil Boyoglu ◽  
Qingwen He ◽  
Gerold Willing ◽  
Seyhan Boyoglu-Barnum ◽  
Vida A. Dennis ◽  
...  

Gold nanoparticles (GNPs) are widely used in biological and clinical applications due to their favorable chemical and optical properties. GNPs can be used for drug delivery to targeted cells. In addition, GNPs serve as ideal probes for biological and cell imaging applications. Recent studies indicate that the size diversity of GNPs plays an important role in targeting cellular components for biomedical applications. In this study, we conducted a series of studies using different sizes of gold nanoparticles, including 3, 10, 25, and 50 nm, to determine the effect of size variations on their intracellular localizations. Our cytotoxicity studies of GNPs into the HEp-2 cells using MTT assay indicated that 3 nm GNPs possess the highest toxicity. We exposed HEp-2 cells with various sizes of gold nanoparticles for different time intervals (1, 2, 4, 12, and 24 h) followed by imaging using scanning electron microscope (SEM) and atomic force microscope (AFM). Our SEM and AFM results showed that, after 1 hr incubation, 3 and 10 nm gold nanoparticles entered the nucleus, whereas 25 and 50 nm particles accumulated around the nucleus. As the time of exposure increased, GNPs entered the cells and accumulated in the cytosol and nucleus based solely on their sizes.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anne-Laure Bailly ◽  
Florian Correard ◽  
Anton Popov ◽  
Gleb Tselikov ◽  
Florence Chaspoul ◽  
...  

Abstract Capable of generating plasmonic and other effects, gold nanostructures can offer a variety of diagnostic and therapy functionalities for biomedical applications, but conventional chemically-synthesized Au nanomaterials cannot always match stringent requirements for toxicity levels and surface conditioning. Laser-synthesized Au nanoparticles (AuNP) present a viable alternative to chemical counterparts and can offer exceptional purity (no trace of contaminants) and unusual surface chemistry making possible direct conjugation with biocompatible polymers (dextran, polyethylene glycol). This work presents the first pharmacokinetics, biodistribution and safety study of laser-ablated dextran-coated AuNP (AuNPd) under intravenous administration in small animal model. Our data show that AuNPd are rapidly eliminated from the blood circulation and accumulated preferentially in liver and spleen, without inducing liver or kidney toxicity, as confirmed by the plasmatic ALAT and ASAT activities, and creatininemia values. Despite certain residual accumulation in tissues, we did not detect any sign of histological damage or inflammation in tissues, while IL-6 level confirmed the absence of any chronic inflammation. The safety of AuNPd was confirmed by healthy behavior of animals and the absence of acute and chronic toxicities in liver, spleen and kidneys. Our results demonstrate that laser-synthesized AuNP are safe for biological systems, which promises their successful biomedical applications.


Author(s):  
Nihad E. Daidzic

A valveless shear-driven micro-fluidic pump design (SDMFP) for hemodynamic applications is presented in this work. One of the possible medical and biomedical applications is in-vivo hemodynamic (human blood circulation) support/assist. One or more SDMFPs can be inserted/implanted into vascular lumens in a form of a stent/duct in series and/or in parallel (bypass duct) to support blood circulation in-vivo. A comprehensive review of various micro-pump designs up to about mid 2000’s is given in [1,2]. Many of micropump designs considered are not suitable for in-vivo or even in-vitro medical/biomedical applications. Operating principles, design, and SDMFP features are given in [3]. A particular design used in cardiovascular applications has no moving valves. SDMFP with Gourney-flap type valves to support high-pressure applications are developed for other applications. SDMFP could be fully bi-directional and can control its operation on the run using embedded microcontrollers and sensors. Estimated efficiency is high with low leakage resulting in low power consumption. Proprietary “fish-scale” surface coating ShearQ™ designs are implemented to improve unidirectional flow pumping efficiency. Bi-directional feature may be especially critical when clogging of blood vessels is detected. By automatically and temporarily switching into the reverse-mode operation and retrogressive flow, while inducing suction-head for a short time periods it is hoped that possibly blood conduits can be cleared/unclogged and the normal forward-flow operation resumed. Such may be an important feature if SDMFP is used in-vivo, such as, in coronary arteries which are prone to clogging leading to cardiac-arrest.


2022 ◽  
Vol 20 (1) ◽  
Author(s):  
Jin Wang ◽  
Di Wang ◽  
Moupan Cen ◽  
Danni Jing ◽  
Jiali Bei ◽  
...  

Abstract Background Cancer is the most serious world's health problems on the global level and various strategies have been developed for cancer therapy. Pillar[5]arene-based supramolecular therapeutic nano-platform (SP/GOx NPs) was constructed successfully via orthogonal dynamic covalent bonds and intermolecular H-bonds with the assistance of glucose oxidase (GOx) and exhibited efficient targeted/synergistic chemo-chemodynamic cancer therapy. Methods The morphology of SP/GOx NPs was characterized by DLS, TEM, SEM and EDS mapping. The cancer therapy efficinecy was investigated both in vivo and in vitro. Results SP/GOx NPs can load drug molecules (Dox) and modify target molecule (FA-Py) on its surface conveniently. When the resultant FA-Py/SP/GOx/Dox NPs enters blood circulation, FA-Py will target it to cancer cells efficiently, where GOx can catalyst the overexpressed glucose to generate H2O2. Subsequently, the generated H2O2 in cancer cells catalyzed by ferrocene unit to form •OH, which can kill cancer cells. Furthermore, the loaded Dox molecules released under acid microenvironment, which can further achieve chemo-therapy. Conclusion All the experiments showed that the excellent antitumor performance of FA-Py/SP/GOx/Dox NPs, which provided an new method for pillar[5]arene-based supramolecular polymer for biomedical applications. Graphical Abstract


Author(s):  
J. D. Shelburne ◽  
Peter Ingram ◽  
Victor L. Roggli ◽  
Ann LeFurgey

At present most medical microprobe analysis is conducted on insoluble particulates such as asbestos fibers in lung tissue. Cryotechniques are not necessary for this type of specimen. Insoluble particulates can be processed conventionally. Nevertheless, it is important to emphasize that conventional processing is unacceptable for specimens in which electrolyte distributions in tissues are sought. It is necessary to flash-freeze in order to preserve the integrity of electrolyte distributions at the subcellular and cellular level. Ideally, biopsies should be flash-frozen in the operating room rather than being frozen several minutes later in a histology laboratory. Electrolytes will move during such a long delay. While flammable cryogens such as propane obviously cannot be used in an operating room, liquid nitrogen-cooled slam-freezing devices or guns may be permitted, and are the best way to achieve an artifact-free, accurate tissue sample which truly reflects the in vivo state. Unfortunately, the importance of cryofixation is often not understood. Investigators bring tissue samples fixed in glutaraldehyde to a microprobe laboratory with a request for microprobe analysis for electrolytes.


Author(s):  
Yasushi P. Kato ◽  
Michael G. Dunn ◽  
Frederick H. Silver ◽  
Arthur J. Wasserman

Collagenous biomaterials have been used for growing cells in vitro as well as for augmentation and replacement of hard and soft tissues. The substratum used for culturing cells is implicated in the modulation of phenotypic cellular expression, cellular orientation and adhesion. Collagen may have a strong influence on these cellular parameters when used as a substrate in vitro. Clinically, collagen has many applications to wound healing including, skin and bone substitution, tendon, ligament, and nerve replacement. In this report we demonstrate two uses of collagen. First as a fiber to support fibroblast growth in vitro, and second as a demineralized bone/collagen sponge for radial bone defect repair in vivo.For the in vitro study, collagen fibers were prepared as described previously. Primary rat tendon fibroblasts (1° RTF) were isolated and cultured for 5 days on 1 X 15 mm sterile cover slips. Six to seven collagen fibers, were glued parallel to each other onto a circular cover slip (D=18mm) and the 1 X 15mm cover slip populated with 1° RTF was placed at the center perpendicular to the collagen fibers. Fibroblast migration from the 1 x 15mm cover slip onto and along the collagen fibers was measured daily using a phase contrast microscope (Olympus CK-2) with a calibrated eyepiece. Migratory rates for fibroblasts were determined from 36 fibers over 4 days.


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