In vivo toxicological evaluation of graphene oxide nanoplatelets for clinical application

Abstract

BackgroundGraphene is considered as a wonder material; it is the strongest material on the planet, super-elastic, and conductive. Its application in biomedicine is huge, with a multibillion-dollar industry, and will revolutionize the diagnostic and treatment of diseases. However, its safety and potential toxicity is the main challenge.MethodsThis study assessed the potential toxicity of graphene oxide nanoplatelets (GONs) in an in vivo animal model using systemic, hematological, biochemical, and histopathological examinations. Normal saline (control group) or GONs (3–6 layers, lateral dimension=5–10 μm, and thickness=0.8–2 nm) at dose rate of 50, 150, or 500 mg/kg were intraperitoneally injected into adult male Wistar rats (n=5) every 48 hours during 1 week to receive each animal a total of four doses. The animals were allowed 2 weeks to recover after the last dosing. Then, animals were killed and the blood was collected for hematological and biochemical analysis. The organs including the liver, kidney, spleen, lung, intestine, brain, and heart were harvested for histopathological evaluations.ResultsThe results showed GONs prevented body weight gain in animals after 21 days, treated at 500 mg/kg, but not in the animals treated at 150 or 50 mg/kg GONs. The biochemical analysis showed a significant increase in total bilirubin, with a significant decrease in triglycerides and high-density lipoprotein in animals treated at 500 mg/kg. Nonetheless, other hematological and biochemical parameters remained statistically insignificant in all GONs treated animals. The most common histopathological findings in the visceral organs were granulomatous reaction with giant cell formation and accumulation of GONs in capsular regions. Also, small foci of neuronal degeneration and necrosis were the most outstanding findings in the brain, including the cerebellum.ConclusionIn conclusion, this study shows that GONs without functionalization are toxic. The future study is a comparison of the functionalized with non-functionalized GONs.

Study of thermomechanical, structural and antibacterial properties of poly(lactic acid) reinforced with graphene oxide nanoparticles via melt mixing

“…According to the tensile test results reported in Table 4, the tensile strength of PLLA increased by ca 21% and ca 25% when 0.4 and 0.8 wt% GO was added (Table 4). This reinforcing effect could be beneficial for applications were as little as 0.4 and 0.8 wt% GO can be incorporated in the polymeric matrix, in order not to be toxic towards human tissues 4,5 . The incorporation of 0.8 wt% GO led to an increase by ca 8% of Young’s modulus value when compared to unreinforced PLLA.…”

“…GO is utilized in nanocomposite fabrication due to its high compatibility with various polymer matrices and has shown its potential for biomedical applications in biosensors, drug delivery and orthopedic implants, attracting research interest in recent years, especially due to its desirable hydrophilicity and antibacterial activity 4 . GO has shown good biocompatibility with red blood cells 5 . The potential toxicity and biocompatibility, however, of GO remain controversial.…”

“…The potential toxicity and biocompatibility, however, of GO remain controversial. In fact, according to Amrollahi‐Sharifabadi et al ., parameters including morphology, size (lateral dimension, thickness and number of layers), concentration, exposure time and surface activity (area, functional groups) can substantially influence the potential toxicity and biocompatibility of GO and, thus, can convert it from a nontoxic to a highly toxic chemical for living organisms 5 . Recent studies have shown that the mechanical properties of composites can be significantly improved with the addition of GO 4 .…”

“…As far as the biocompatibility of graphene and its derivatives is concerned, their tribological properties in terms of low friction, high wear resistance and self‐lubrication seem very promising 5 . Hence, there should be great potential for GO to be used for engineering of PLLA‐based biomaterials for high‐performance and long‐life medical devices, including various body implants and scaffolds.…”

“…In the study reported here, GO/PLLA composites were prepared via a melt‐extrusion process, which was found adequate for properly dispersing the nanoparticles within the polymeric matrix, thus avoiding the use of toxic solvents necessary for running a solution process. Based on previous studies, 4‐6,10 the content of GO in the nanocomposites was such as to ensure nontoxicity for biomedical applications and act in favor of PLLA crystallization that controls its other properties. Subsequently, the isothermal crystallization kinetics of the nanocomposites were investigated using DSC to examine the influence of GO on the crystallization behavior of PLLA.…”