Inhaling an ultra-pure form of the ‘wonder material’ graphene did not produce any short-term adverse effects on lung and cardiovascular function in a small group of healthy volunteers. The first-in-human study opens the door to developing a novel targeted drug delivery method to treat diseases such as cancer.
The main goal of designing an optimized drug delivery system is to deliver therapeutic agents to diseased tissue in a controllable manner while producing few side effects on healthy tissue. Because of its chemical and mechanical stability, hydrophilic properties, high surface area and biocompatibility, graphene oxide (GO), the oxidized form of the ‘wonder material’ graphene, has been proposed for such a purpose.
However, limited and inconsistent evidence exists about whether GO is safe to use in humans, mostly because of the many different sources of the material and their notable variability in dimensions and chemical properties. Now, a first-in-human study conducted by researchers from the University of Edinburgh, Scotland, found that inhaling ultra-pure GO produced no adverse effects.
“Nanomaterials such as graphene hold such great promise, but we must ensure they are manufactured in a way that is safe before they can be used more widely in our lives,” said Mark Miller, one of the study’s corresponding authors. “Being able to explore the safety of this unique material in human volunteers is a huge step forward in our understanding of how graphene could affect the body. With careful design, we can safely make the most of nanotechnology.”
The researchers synthesized thin, highly purified metal- and endotoxin-free GO nanosheets in two dimensions: small GO (s-GO) and ultra-small GO (us-GO). The nanosheets were then aerosolized for inhalation via a face mask. Fourteen healthy volunteers inhaled either a single dose of GO or filtered air for two hours while intermittently cycling to standardize respiratory rates between individuals. A few weeks later, participants returned to the clinic for repeated controlled exposures to a different size GO or clean air, for comparison.
The researchers found that inhalation of GO was not associated with any acute adverse effects on participants’ lung or cardiovascular function or systemic inflammation. A “mild increase” in thrombogenicity, the tendency of a material to cause clotting when it comes in contact with the blood, was seen in an ex vivo model of vascular injury, highlighting the need for further studies to more fully evaluate the actions of inhaled manufactured nanomaterials.
The researchers acknowledge the study's limitations, namely, that the number of participants was small and that they only tested a single dose of GO. It may be that participant numbers were insufficient to detect more subtle effects of GO inhalation or that higher concentrations or longer exposure durations could produce effects that weren’t apparent in the current study. Nonetheless, they say, the study represents a big step towards a comprehensive risk assessment of the use of GO in the biomedical space.
“This is the first-ever controlled study involving healthy people to demonstrate that very pure forms of graphene oxide – of a specific size distribution and surface character – can be further developed in a way that would minimize the risk to human health,” said Kostas Kostarelos, another corresponding author.
However, the study raises a significant issue: The feasibility of discoveries like this. For the benefits of graphene and GO to be realized, it requires production in massive amounts at a low cost. So far, mass-scale production with low cost has remained a distant dream.
The study was published in the journal Nature Nanotechnology.
Source: University of Edinburgh
