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

Abstract

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.

Pharmacokinetics of PEGylated Gold Nanoparticles: In Vitro—In Vivo Correlation

“…Polyethylene glycol (PEG)-coated gold NPs (PEG-AuNPs) with a core size of 10.5 ± 0.8 nm and hydrodynamic diameter of 13.1 ± 3.0 nm were synthesized and characterized in depth using various physicochemical methods. Basic physicochemical characteristics of PEG-AuNPs have already been published [ 24 ] and can be found in the Supplementary Materials (SEM image, Figure S1 ; UV/Vis spectra, Figure S2 ; size and zeta potential distribution curves, Figure S3 ). The same stock of PEG-AuNPs was used in both in vitro and in vivo experiments.…”

“…After reaching confluence of 75–80%, cells were exposed to PEG-AuNPs at a concentration of 5 µg mL −1 . This working concentration was prepared as previously described [ 24 , 25 ]. The kinetics of PEG-AuNPs uptake into individual cell lines, representing surrogate in vitro models of particular organs, was investigated at several time-point intervals (1 h, 2 h, 4 h, 6 h, 9 h, 16 h, 24 h, and 48 h) after single-dose application.…”

“…Then, cells were detached from the bottom of the P. dishes by trypsinization, pooled (3 P. dishes per time interval), spun down, and the pellet was frozen and kept at −20 °C until analysis by graphite furnace atomic absorption spectrometry (GFAAS). The conditions of samples’ mineralization and subsequent GFAAS analysis were the same as those used for in vivo study [ 24 ].…”

“…The experiment was carried out on six to eight-week-old male Wistar rats. The design of the in vivo experiment and PEG-AuNPs administration have already been published [ 24 ]. In brief, male Wistar rats (b. w. 210–230 g) were injected via tail vein with a single dose of PEG-AuNPs (0.70 mg kg −1 ) suspension and sacrificed after 1 h, 4 h, 24 h, 7 days, and 28 days post-exposure.…”

“…A non-mechanistic model for NP translocation was applied to in vitro cell cultures and the resulting parameters were then utilized for predicting the biodistribution in vivo. Finally, the simulated biodistribution curves were compared with data published in our previous study [ 24 ].…”