University Times

Pitt researchers hope to begin clinical trials this summer of a new inhaler that would give soldiers a better way of self-administering an antidote for nerve-agent poisoning.

Scientists from Pitt and MicroDose Technologies, Inc. of New Jersey are sharing a $1.52 million grant this year from the U.S. Department of Defense to develop the inhaler.

It would be a smaller, lighter, more efficient and environmentally benign replacement for current inhalers that use chlorofluorocarbons (CFCs) to propel the antidote, said Tim Corcoran, a Pitt research professor of medicine and bioengineering who is working on the project.

Recovery from nerve agent intoxication is a prolonged process requiring an extended period of hospitalization and therapy, Corcoran pointed out.

“Currently, soldiers exposed to nerve agents like sarin and tabun use an auto-injector syringe to give themselves an antidote out on the battlefield,” he said. “When they reach a field hospital, they’re given inhalers that they use, under the supervision of a nurse or doctor, over the next few days to deliver the antidote directly to the lungs.

“It takes a lot of the antidote — called atropine — over a prolonged period of time to overcome the effects of nerve gas.”

Rather than employing ozone-depleting CFCs, the inhaler being developed here would use a piezo vibrator, which converts electrical energy to mechanical motion that is then transferred to a dry powder. This vibration de-aggregates the powder, forming an aerosol that directly deposits in the lungs when inhaled, where it dissolves and is absorbed into the bloodstream.

But making the aerosol particles the right size can be tricky.

“We have to create an aerosol that is small enough to get past natural filters in the nose, mouth and throat but large enough to deposit deep into the lungs where the blood and air interact with each other,” Corcoran explained.

“Lungs are structured in such a way that it’s very difficult for particulate matter to get down into these deep surfaces.”

To be effective, aerosol atropine particles each will have to measure between 1 and 1.5 microns, a micron being one-thousandth of a millimeter.

The new inhalers would continue as a secondary treatment for nerve-agent poisoning. “We’re not trying to replace the auto-injector syringe. That would still be the first treatment a soldier would use,” Corcoran said.

Testing of the new inhaler in humans will take place at UPMC Presbyterian Hospital, probably early this summer, he said.

“Obviously, we can’t test this under the actual conditions in which it’s going to be used. We can’t expose people to nerve gas,” noted Corcoran. “So, we’ll rely on other techniques that will let us see where the drug is deposited in the lungs and how quickly it reaches the ideal concentration in the bloodstream.”

Atropine itself is harmless, so study participants can safely use the inhaler to take the antidote. A radioisotope version of atropine will enable researchers to trace where it’s deposited in the lungs. Blood tests will measure concentrations of atropine in participants’ bloodstreams.

Corcoran used similar techniques to measure deposited doses of an aerosol form of the anti-rejection drug cyclosporine, which a research team led by Pitt investigator Aldo Iacono developed for use by lung-transplant patients.

Iacono, an associate professor of medicine and surgery, said: “Our objective is to demonstrate that this new [dry powder inhaler] technology can improve the effectiveness of these antidotes by significantly reducing the time for the treatment to reach its peak concentration in the blood and by improving the reliability of the dose delivered to the soldier.”

Taking advantage of aerosol medicine expertise at the University and UPMC, other Pitt researchers are working on aerosol antibiotics and aerosol-delivered drugs for asthma, sarcoidosis and cystic fibrosis.

Pitt and MicroDose Technologies were brought together to co-develop the anti-nerve agent inhaler by U.S. Rep. John Murtha (D-Johnstown), Corcoran said.

“Representative Murtha was already familiar with MicroDose and, obviously, he knew about the University of Pittsburgh,” said Corcoran. “He found out about our research on aerosol drugs through Jeanne Stoner,” head of federal relations for Pitt.

Murtha helped to secure the project’s $1.52 million funding for this year and is pursuing additional appropriations to keep the research going, according to Corcoran, who said he’s confident that Congress will approve such funding.

“You don’t want to start into a project like this and not finish it,” he said.

As the project proposal noted, “The increased risk to American forces in the field to the threat of chemical and biological weapons is well recognized and documented. This substantial and serious risk from classical chemical agents, e.g. vesicants, blood agents, respiratory agents and nerve agents requires new research and medical countermeasures, including enhancement of the method of delivery embodied in the aging auto-injector technology.”

Corcoran predicted that the inhaler will be ready for battlefield use in about four years.

“Like anything else that needs approval from the FDA, it’s a long and involved process,” he said.

—Bruce Steele