Breathing in metal: Dissolution testing and new metal nanoparticles, will it become mandatory?

More industrial processes than ever are using nanoparticles. Yet many questions remain about the health consequences of inhaling them. Not just in our lungs but at a cellular, even genetic level. Now, using Inhalation Sciences equipment, Karolinska Institutet doctoral researcher Sarah Mccarrick is investigating how inhaled metal nanoparticles impact us.

Nanoparticles offer a world of advantages to industrial process manufacturers. But what happens when we breathe them in? Inhalation researcher Sarah Mccarrick has joined the Institute of Environmental Medicine team at Karolinska Institutet, under Assoc. Professor Hanna Karlsson, to assess the toxicology and dissolution profiles of metal nanoparticles.

“Exposure to nanoparticles has increased hugely in the last decade,” says Mccarrick. “And in particular it is the ever-increasing number of different types of nanoparticles that makes it hard for researchers to keep up. Because of this there is a great demand for assessing risks without having to test every single particle individually, in costly, time-consuming and ethically questionable animal studies. We’re seeing new animal-free methods like cell culturing and computational modelling becoming increasingly popular.”

Mccarrick has been using two such methodologies from ISAB: the in vitro simulation tool DissolvIt ^® and the in vitro Air Liquid Interface system XposeALI ^® to run her dissolution tests. “There are other methods to study dissolution,” she says. “But mostly using very static conditions. As we all know though, the lung is a complex organ, especially its Air Liquid Interface. The fact that both systems are dynamic, that they mimic the dynamic perfusion of the in vivo setting is vital. Plus, the optical microscopy of DissolvIt ^®, actually being able to see the dispersal, is important. It definitely adds extra dimensions to your research.”

Nanoparticles in the cells: Making dissolution testing mandatory

Because nanoparticles are so small they can penetrate much deeper into the lung, which can lead to greater distribution of toxic particulates throughout the body. Unlike micro particles they are so small they can actually be taken up by the cells themselves too.

“Uptake and distribution of nanoparticles in the body can differ widely” says Mccarrick. “So dissolution testing in the lungs on a cellular level is crucial for assessing the risk of toxicity. Do nanoparticles dissolve in the lungs to further be taken up as ions, for example? Or do they remain in particle form? If dissolution occurs quickly maybe they would have the same effects as the ions themselves. If not you would have to consider them as a completely different risk. It’s dissolution testing that answers these questions.”

“Eventually I’d hope to see dissolution testing as a mandatory part of toxicological testing for all inhalables,” she says “as we produce even greater numbers of new particulate materials. I think we’ll see tougher more demanding regulations from governments and corporations around the quantity and quality of airborne pollution research. Dissolution of nanoparticles is a vital factor in being able to predict and understand the behaviour and fate of nanoparticles in our bodies, and it’s an essential part of being able to group nanoparticles for risk assessment.”