The threat of injury and even death hangs over the head of most active men and women in the armed forces. However, the treatment for some injuries can be life-threatening as well. Soldiers unfortunate enough to be injured in the line of duty are usually given morphine for pain relief in the field. However, morphine also depresses normal breathing and blood pressure, sometimes to near-fatal levels. So medics need a short-acting drug that aids normal respiration and heart beat, but in doses that still allow effective morphine pain relief. It’s a bit like a dangerous ‘balancing act’, made worse because it’s often performed under extreme circumstances. Using nanotechnology, University of Michigan (U-M) scientists have developed a combination drug that promises a safer, more precise way for medics and fellow soldiers in battle situations to give a fallen soldier morphine, together with a drug that limits morphine’s dangerous side effects.

Nanotechnology is used to create ultra-small polymer particles capable of carrying the drugs into the body. The scientists say the development of the combination drug makes it possible to create a precise feedback system that can safely regulate release of the drugs aboard the nanoparticles.

The scientists at the Michigan Nanotechnology Institute for Medicine and Biological Sciences University of Michigan 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. Their full results are in the September issue of Bioorganic & Medicinal Chemistry Letters.

The long-range goal of the research is to develop a practical method that medics or soldiers could administer, perhaps using an auto-injector device. And it is hoped that this type of treatment could have far-reaching possibilities. Apart from better, safer treatment for injured solders, “this system could improve pain management for millions of patients with chronic illnesses,” says Prof James R. Baker Jr., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS) and the study’s senior author.

An intricate search

U-M chemists screened several compounds searching for a drug that could release or become another drug. In this case, they wanted one that could convert to Naloxone, a drug now used to counter morphine’s effects, but would activate only when blood oxygen levels drop too low.

Using human plasma in laboratory tests, one ‘pro drug’ was successfully identified as being able to sense oxygen blood levels and turned on or off as needed.

“When respiratory distress is too severe, that will trigger release of Naloxone, the antagonist (morphine-suppressing) drug. When the oxygen blood levels go up, that will stop the action of the antagonist drug and more morphine will be available,” says Baohua Huang, Ph.D., the study’s first author and a research investigator at the Michigan Nanotechnology Institute and in Internal Medicine.

MNIMBS scientists are conducting further extensive studies before testing on humans proceeds.