UNC, Russian Scientists Create Biological Shield against Nerve Gas, Pesticides
April 3, 2017
Eshelman School of Pharmacy
Scientists at the University of North Carolina at Chapel Hill and Moscow State University have created a new way to package and deliver a potent enzyme that can reverse — and even prevent — poisoning by pesticides and nerve gas, including VX and sarin, which has been used worldwide as a chemical weapon and estimated to be 26 times more deadly than cyanide.
The team, led by UNC-Chapel Hill’s Alexander “Sasha” Kabanov, Mescal S. Ferguson Distinguished Professor, figured out how to wrap the powerful enzyme, called organophosphorus hydrolase, in a tiny nanoparticle, which could be taken before, during or after exposure to organophosphate-based toxins.
“It could provide complete protection even if injected many hours before exposure to a lethal dose of toxin,” said Kabanov, who is also director of the Center for Nanotechnology in Drug Delivery at the UNC Eshelman School of Pharmacy. “The enzyme is so effective that just one molecule of the enzyme can decompose several thousand of molecules of toxin every second, so the nanozyme appears to be effective at much lower doses than other potential treatments.”
Currently, animals and humans can be treated only after exposure. If caught early, treatment is very effective at reversing symptoms, but the knockdown on some of these toxins is so fast that there is not enough time to respond or the toxin’s effects are not realized until treatment cannot reverse damage. For something like VX or sarin gas, it’s a matter of seconds before victims can no longer treat themselves.
Working with rats, Kabanov and his team showed that the nanozymes circulated for at least 17 hours after a single injection, but they believe that time can be extended with more work. One approach would be to make the nano-packaging, which is currently 25 to 100 nanometers in diameter, even smaller. The smaller the packaging, the better it is to hide it from the body’s immune system, which tends to see large molecules like the life-saving enzyme as a foreign invader to be attacked and cleared.
The drug atropine, in combination with pralidoxime, has been the first line of treatment for organophosphate poisoning since World War II. However, atropine and pralidoxime cannot be given in advance to protect against poisoning and introduces a big, sometimes lethal, shock to the body.
“Two milligrams of atropine is a typical starting dose to counter organophosphate poisoning, and it will make your heart to nearly jump out of your chest,” said Greene Shepherd, a specialist in clinical toxicology and emergency preparedness at the UNC Eshelman School of Pharmacy who was not involved in the research. “A healthy person could probably survive it, but having something that could be administered in advance of exposure would be a very big deal.”
The team’s discovery was published in the Journal of Controlled Release.
January 23, 2023