University of Pittsburgh Receives Department of Defense Grant to Develop Delivery System for Nerve Agent Poisoning Antidote
PITTSBURGH, October 13, 2003 American troops may soon have a better line of defense against chemical weapons as a result of research beginning at the University of Pittsburgh School of Medicine.
The Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh School of Medicine has received a $1.52 million grant from the U.S. Department of Defense to co-develop a dry powder inhaler (DPI), which would administer an antidote for nerve agent poisoning. The system will allow more efficient self-administration of the drug atropine by American forces while under the care of military healthcare professionals.
The research will be conducted in collaboration with MicroDose Technologies, Inc., of Monmouth Junction, N.J., and will use MicroDoses proprietary pulmonary delivery technology.
Chemical and biological agents pose a considerable threat to American forces and potentially to other military personnel and civilians. The development of a new antidote delivery system is a crucial step in protecting personnel from these threats, said Augustine Choi, M.D., chief of the Division of Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh and principal investigator of the project. This grant will allow us to develop and test a new and improved method of protection from the effects of chemical warfare agents.
The Armys current inhaler technology depends on chlorofluorocarbons (CFCs), which are being phased out due to environmental concerns. The new drug delivery system contains no propellant and is based on DPI technology developed by MicroDose.
Our objective is to demonstrate that this new 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, said Aldo Iacono, M.D., associate professor of medicine and surgery at the University of Pittsburgh School of Medicine, who has over ten years of experience in developing aerosol immunosuppressants for lung transplant recipients.
The MicroDose DPI technology uses a piezo vibrator, which converts electrical energy to mechanical motion that is then transferred into the 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. By controlling the amplitude and frequency of the vibration, the DPI can be used for various compounds.
Atropine is a drug that has, among other uses, an ability to treat the effects of certain poisons and nerve agents such as tabun, sarin, soman, cyclosarin and VX. The current standard treatment for exposure to one of these agents includes intramuscular injection of atropine sulfate followed by an oxime using an autoinjector syringe. The initial research will focus on the development of a dry powder form of atropine including micronization, stability testing and development of a radioisotope-labeled form of the medication for use during studies.
We believe that the use of a dry powder inhaler will result in more efficient delivery of the medication compared to the device the Army is using now. This should mean faster relief from the symptoms, said Tim Corcoran, Ph.D., research assistant professor of medicine and bioengineering at the University of Pittsburgh.
Dr. Corcoran is co-investigator in the project and a biomedical engineer with extensive experience in the development of aerosol drugs and aerosol drug delivery devices.
Inhaled medications have a long history of use in the treatment of respiratory diseases and the administration of medications to the bloodstream through the lungs has been successfully demonstrated in recent years. The surface area on the inside of the lungs is approximately 143 square-meters, approximately the same surface area as a tennis court, providing considerable access to the bloodstream. The blood interacts with the air spaces in the lungs through a boundary that is only 2 cell layers thick, allowing for the quick passage of inhaled medications into the bloodstream, according to Dr. Corcoran.
Also participating in the study is Frank Torok, M.D., an assistant professor of radiology at Pitt and a nuclear medicine physician. Dr. Torok's duties include the administration of radioisotope medications and the interpretation of images generated by gamma cameras.
Gamma camera technology can be used along with radioactive forms of some medications to create a picture of where an inhaled aerosol deposits in the lungs. University of Pittsburgh investigators have previously used this technique to evaluate the effectiveness of inhaled medications, Dr. Torok said.
Recovery from nerve agent intoxication is a prolonged process requiring an extended period of hospitalization and therapy, which may include additional atropine administrated via an inhalation route under the supervision of medical professionals.
MicroDose Technologies, Inc., based in Monmouth Junction, N.J., is a privately held drug delivery company developing advanced pulmonary, solid oral dosage and needle-free transdermal products for the pharmaceutical industry. The MicroDose DPI is a handheld, low cost, breath-activated device, which makes novel use of piezo electronics to efficiently deliver a broad range of compounds independent of inhalation effort. The device is the first totally electronic DPI and represents the next generation in inhaler technology both in performance and ease of use.