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Nanoparticle-based battlefield pain treatment moves step closer
September 25, 2009University of Michigan 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 both morphine and a drug that limits morphine's dangerous side effects.
They use nanotechnology to devise ultra-small polymer particles capable of carrying the drugs into the body. The development of the combination drug makes possible 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 report their results in the September issue of Bioorganic & Medicinal Chemistry Letters.
Context
Soldiers injured in combat typically receive morphine as soon as possible to relieve pain. Morphine, however, also depresses normal breathing and blood pressure, sometimes to life-threatening levels. So medics need to give a short-acting drug that aids normal respiration and heart beat, but in doses that still allow the morphine to relieve pain effectively. Today, achieving that balance is a challenge outside a hospital.
The combination drug that U-M scientists have developed promises to make balanced treatment possible even in combat zones, says James R. Baker, Jr., M.D., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS) and the study's senior author.
"This system could improve pain management for millions of patients with chronic illnesses," says Baker, Ruth Dow Doan Professor and allergy division chief in the U-M Department of Internal Medicine.
The long-range goal of the research, funded by the U.S. Defense Advanced Research Projects Agency, is to develop a practical method that medics or soldiers themselves could administer, perhaps using an auto-injector device.
Research details
U-M chemists screened several compounds to search for a successful "pro drug," a drug that can 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.
In laboratory tests using human plasma, one pro drug successfully sensed oxygen 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.
What's next
MNIMBS scientists are proceeding with animal studies of the pro drug's effects and will develop a dendrimer that can carry the pro drug and morphine, using a dendrimer platform technology previously developed at U-M. They hope to advance to more animal and eventually human studies.
Patents/Disclosures: Patent applications have been filed on related U-M dendrimer inventions.
Additional U-M authors: Shengzhuang Tang, M.S., MNIMBS; Ankur Desai, M.S., MNMBS; Xue-min Cheng, Ph.D., adjunct research associate professor, Department of Internal Medicine and MNIMBS; Alina Kotlyar, M.S., MNIMBS; Abraham Van Der Spek, M.D., associate professor of anesthesiology, and Thommey P. Thomas, Ph.D., research assistant professor, Department of Internal Medicine and MNIMBS.
Citation: Bioorganic & Medicinal Chemistry Letters, Volume 19, Issue 17, 1 September 2009, pp. 5016-5020
Funding: Defense Advanced Research Projects Agency, part of the U.S. Department of Defense.
University of Michigan Health System
Context
Soldiers injured in combat typically receive morphine as soon as possible to relieve pain. Morphine, however, also depresses normal breathing and blood pressure, sometimes to life-threatening levels. So medics need to give a short-acting drug that aids normal respiration and heart beat, but in doses that still allow the morphine to relieve pain effectively. Today, achieving that balance is a challenge outside a hospital.
The combination drug that U-M scientists have developed promises to make balanced treatment possible even in combat zones, says James R. Baker, Jr., M.D., director of the Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS) and the study's senior author.
"This system could improve pain management for millions of patients with chronic illnesses," says Baker, Ruth Dow Doan Professor and allergy division chief in the U-M Department of Internal Medicine.
The long-range goal of the research, funded by the U.S. Defense Advanced Research Projects Agency, is to develop a practical method that medics or soldiers themselves could administer, perhaps using an auto-injector device.
Research details
U-M chemists screened several compounds to search for a successful "pro drug," a drug that can 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.
In laboratory tests using human plasma, one pro drug successfully sensed oxygen 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.
What's next
MNIMBS scientists are proceeding with animal studies of the pro drug's effects and will develop a dendrimer that can carry the pro drug and morphine, using a dendrimer platform technology previously developed at U-M. They hope to advance to more animal and eventually human studies.
Patents/Disclosures: Patent applications have been filed on related U-M dendrimer inventions.
Additional U-M authors: Shengzhuang Tang, M.S., MNIMBS; Ankur Desai, M.S., MNMBS; Xue-min Cheng, Ph.D., adjunct research associate professor, Department of Internal Medicine and MNIMBS; Alina Kotlyar, M.S., MNIMBS; Abraham Van Der Spek, M.D., associate professor of anesthesiology, and Thommey P. Thomas, Ph.D., research assistant professor, Department of Internal Medicine and MNIMBS.
Citation: Bioorganic & Medicinal Chemistry Letters, Volume 19, Issue 17, 1 September 2009, pp. 5016-5020
Funding: Defense Advanced Research Projects Agency, part of the U.S. Department of Defense.
University of Michigan Health System
Morphine Current Events and Morphine News RSSCommon pain relief medication may encourage cancer growth
Although morphine has been the gold-standard treatment for postoperative and chronic cancer pain for two centuries, a growing body of evidence is showing that opiate-based painkillers can stimulate the growth and spread of cancer cells.
Chronic pain treatments work better together, says Queen's anesthesiologist
People who suffer from debilitating neuropathic pain may get more relief and sleep better by combining two commonly-prescribed drugs.
Infant pain, adult repercussions
Scientists at Georgia State University have uncovered the mechanisms of how pain in infancy alters how the brain processes pain in adulthood.
Researchers explore long-term adolescent vulnerability to drugs
As part of efforts to understand drug abuse, Georgia State University researchers are finding that adolescent rats appear to be less vulnerable to the long-term effects of withdrawal and relapse in certain types of drug use than rats that take the drugs in adulthood.
Researchers find genetic link between physical pain and social rejection
UCLA psychologists have determined for the first time that a gene linked with physical pain sensitivity is associated with social pain sensitivity as well.
Chinese acupuncture affects brain's ability to regulate pain, UM study shows
Acupuncture has been used in East-Asian medicine for thousands of years to treat pain, possibly by activating the body's natural painkillers. But how it works at the cellular level is largely unknown.
Fish may actually feel pain and react to it much like humans
Fish don't make noises or contort their faces to show that it hurts when hooks are pulled from their mouths, but a Purdue University researcher believes they feel that pain all the same.
Hebrew University researchers show how morphine can be given more effectively
Researchers at the Hebrew University of Jerusalem have found a way to maintain the pain-killing qualities of morphine over an extended period of time, thus providing a solution for the problem of having to administer increasing dosages of the drug in order to retain its effectiveness.
Mayo Clinic study suggests those who have chronic pain may need to assess vitamin D status
Mayo Clinic research shows a correlation between inadequate vitamin D levels and the amount of narcotic medication taken by patients who have chronic pain.
New guidelines for prescribing opioid pain drugs published
A prestigious panel of pain-management experts representing the American Pain Society (APS) www.ampainsoc.org and the American Academy of Pain Medicine (AAPM) has published the first comprehensive clinical practice guideline to assist clinicians in prescribing potent opioid pain medications for patients with chronic non-cancer pain.
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