Nanoparticles may provide safe pain control on the battlefield

University of Michigan scientists have received a pilot grant of nearly $1.3 million from the Defense Advanced Research Projects Agency to test whether nanoparticles can solve a pressing problem in battle zones like Iraq: how to administer sustained, safe doses of the most effective painkillers to injured soldiers, long before they can reach expert medical help.

The ultimate goal is to develop tiny drug-bearing particles that a fellow soldier —or perhaps the injured soldier himself —could inject with a pen-like device, even in the heat of combat. That would solve one of the challenges now. Morphine, an effective painkiller that the military commonly uses for the acute pain of battle injuries, currently needs to be injected by skilled medical personnel and has to be monitored carefully to control its troublesome tendency to suppress normal breathing.

“This proposal provides an approach to achieve sustained, safe pain control on the battlefield,” says the U-M research team's leader, James R. Baker, Jr., M.D., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences.

“It uses different medicines coupled to polymers to release drugs and antidotes to provide adequate pain relief while avoiding complications. If successful, it could markedly improve the treatment of soldiers in the field,” says Baker, the Ruth Dow Doan Professor of Internal Medicine in the U-M Medical School.

The work could have a broad impact. In the war in Iraq, more than 26,900 U.S. soldiers have been wounded in action as of late July. It's known that battlefield pain, if not relieved adequately, can lead to post-traumatic stress disorders.

A large multidisciplinary team of U-M scientists will use the grant to design multipurpose nanoparticles and test how well they perform several tasks under simulated physiological conditions in the laboratory. Ultimately, they want the particles to be able to:

• control the release of morphine over extended periods before a soldier can be evacuated to a military acute care facility,
• continuously monitor the soldier's breathing and if needed, release a drug called Naloxone that is used to counter morphine's effects on breathing.

The team, which includes synthetic, analytical and medicinal chemists, will expand on the use of dendrimer platforms, a technology previously developed at the U-M. They will design ultra-small polymer particles called dendrimers capable of carrying morphine and Naloxone into the body and releasing them in controlled amounts. They will develop sensors that the dendrimers will also carry to monitor a soldier's respiration and trigger Naloxone release, or halt it, as needed.

If the concept proves successful after the first year of in vitro studies, Baker and his team want to apply for continued DARPA funding to proceed with animal and eventually human studies.

Other U-M team members include Abraham F. L. Vanderspek, M.D., associate professor of anesthesiology; Brent Ward, MD, DDS, FACS, assistant professor of oral and maxillofacial surgery and program director of Oncologic Maxillofacial/Head & Neck Surgery; Xue-min Cheng, Ph.D., research associate professor, Department of Internal Medicine and M-NiMBS; a medicinal chemist, Rameshwer Shukla, Ph.D., who is a research investigator in the Department of Internal Medicine and M-NiMBS; a medicinal chemist, Xiangyang Shi, Ph.D., who is a research investigator in the Department of Internal Medicine and M-NiMBS; a polymer chemist, Baohua Huang, Ph.D., who is a research investigator in the Department of Internal Medicine and M-NiMBS; a polymer chemist, Xiangdong Bi, Ph.D., Department of Internal Medicine and M-NiMBS; an organic chemist, Mark M. Banaszak Holl, Ph.D., professor of chemistry, applied physics and biophysics in the U-M College of Literature, Science, and the Arts, and of macromolecular science and engineering in the U-M College of Engineering; Ankur Desai, M.S., Department of Internal Medicine and M-NiMBS; an analytical chemist, Thommey P. Thomas, Ph.D., research assistant professor, Department of Internal Medicine and M-NiMBS; Bradford G. Orr, Ph.D., professor of physics in LS&A, director of the Academic Program in Applied Physics, and associate director of M-NiMBS; Alina Kotlyar, M.S., Department of Internal Medicine and M-NiMBS; and Thomas Dunham, B.S., of U-M Maxillofacial Surgery.

For more information on the U-M Nanotechnology Institute for Medicine and Biological Sciences, visit http://www.nano.med.umich.edu/

Funding for the study comes from the Defense Advanced Research Projects Agency, part of the U.S. Department of Defense.

Patent applications have been filed on related U-M dendrimer inventions, which have been exclusively licensed to Avidimer Therapeutics, an Ann Arbor based biotech company in which Dr. Baker has a financial interest.