Biodistribution of a High Dose of Diamond, Graphite, and Graphene Oxide Nanoparticles After Multiple Intraperitoneal Injections in Rats

Abstract

Carbon nanoparticles have recently drawn intense attention in biomedical applications. Hence, there is a need for further in vivo investigations of their biocompatibility and biodistribution via various exposure routes. We hypothesized that intraperitoneally injected diamond, graphite, and graphene oxide nanoparticles may have different biodistribution and exert different effects on the intact organism. Forty Wistar rats were divided into four groups: the control and treated with nanoparticles by intraperitoneal injection (4 mg of nanoparticles/kg body weight) eight times during the 4-week period. Blood was collected for evaluation of blood morphology and biochemistry parameters. Photographs of the general appearance of each rat's interior were taken immediately after sacrifice. The organs were excised and their macroscopic structure was visualized using a stereomicroscope. The nanoparticles were retained in the body, mostly as agglomerates. The largest agglomerates (up to 10 mm in diameter) were seen in the proximity of the injection place in the stomach serous membrane, between the connective tissues of the abdominal skin, muscles, and peritoneum. Numerous smaller, spherical-shaped aggregates (diameter around 2 mm) were lodged among the mesentery. Moreover, in the connective and lipid tissue in the proximity of the liver and spleen serosa, small aggregates of graphite and graphene oxide nanoparticles were observed. However, all tested nanoparticles did not affect health and growth of rats. The nanoparticles had no toxic effects on blood parameters and growth of rats, suggesting their potential applicability as remedies or in drug delivery systems.

Toxicity studies of six types of carbon nanoparticles in a chicken-embryo model

“…17 This is the same dose that was administrated to laboratory rats in our previous studies. 29,37 The CNPs were resuspended in WFI, which is commonly used for diluting or dissolving drugs for parenteral injection (including intravenous, intra-arterial, intramuscular, or subcutaneous injections). 38 WFI properties differ from Milli-Q water, and might explain the disparity between this work and previous research on GFM embryotoxicity.…”

“…16,17 A GNP solution was also positively charged (35.57 mV), which is characteristic of GNPs despite the solvent, especially considering that in sterile saline solution at the same concentration, it was also positively charged (12.5 mV). 29 Other CNPs were negatively charged, but we expected that interactions with egg albumin would alter the ζ-potential to around -9 mV, as has been previously demonstrated. 16 For GNPs and rGO, stability improved in saline solution relative to Milli-Q water.…”

“…In order to prepare rGO, a water suspension with 50 mg of lGO was used as described in our previous report. 4 sGO flakes were prepared by a modified Hummers method, as described previously, 29 and ranged in size from 8 to 25 nm. NP powders were resuspended in water for injection (WFI; Aqua Pro injection; Polpharma, Starogard Gdański, Poland) to a concentration of 500 µg/mL and sonicated at 550 W/m 2 for 1 hour in an ultrasonic bath (Sonorex Super RK 514H; Bandelin Electronic, Berlin, Germany).…”

“…Similar results have been reported previously. 4,[16][17][18]29,37 However, because blood serum homeostasis is tightly controlled, the lack of effects on serum indices might not necessarily reflect a lack of toxic effects. Therefore, we also examined the toxic effects of CNPs by screening for oxidative damage status in the livers of chicken embryos.…”

Rapid Adsorption of Proinflammatory Cytokines by Graphene Nanoplatelets and Their Composites for Extracorporeal Detoxification

“…The liver, as the main organ for detoxification, has been reported to accumulate nanoparticles after their injection in the bloodstream [25,26]. A human hepatic epithelial cell line HepG2 (CRL-119976, ATCC5, VA, USA) was used for the assessment of GNP cytotoxicity, with silver nanoparticles as a positive control due to their widely reported cytotoxicity and hepatocytotoxicity [27,28].…”