Faculty Spotlight: Michael Jay, PhD

The application of pharmaceutical approaches to solve problems related to nuclear imaging and therapy, and the use of radioanalytical approaches to solve problems encountered in the development of novel formulations and drug delivery systems.

When people are contaminated with certain radioactive materials, they can be treated with diethylene triamine pentaacetic acid (DTPA), which binds to the radioactive material in the body, allowing it to be expelled through urine.

The interest in DTPA has increased in recent years as fears about dirty bombs have spiked since 9/11. A dirty bomb — an explosive device designed to disperse radioactive material — has not yet been detonated, but significant and verifiable threats have been reported in the US and abroad, and experts believe such a device is not likely to be powerful enough to cause mass destruction. However, if a dirty bomb is set off, the fear of radioactive contamination could cause public panic. For this reason, dirty bombs are sometimes referred to as “weapons of mass disruption”.

Michael Jay, PhD, a professor at the UNC Eshelman School of Pharmacy, is conducting research to make DTPA more readily available to people exposed to radioactive material by an accident or a dirty bomb. He is working on an oral form of the drug, which, if successful, will be added to the Center for Disease Control and Prevention’s Strategic National Stockpile.

When administered within hours after contamination, DTPA is very effective in eliminating radioactive material from the body. However, the drug is currently only available in IV form, which makes producing, storing, and administering the drug more complicated.

“Injectable forms don’t make good products for a national stockpile because they are expensive to make,” Jay says. “They also have to be sterile, the shelf life is shorter, and you need a professional to administer it.

“Everything is easier with an oral form. Administering would be easier, storing it would be easier, manufacturing would be cheaper.”

However, the challenge in producing an oral dose of DTPA has been its low bioavailability—the percentage of a dose that gets absorbed, unchanged, into the blood. An IV dose has a 100 percent bioavailability, whereas less than 1 percent of an orally administered dose of DTPA gets absorbed.

Since 2005, Jay has received a $5.2 million grant from the National Institute of Allergy and Infectious Diseases to develop an oral form of DTPA. The goal: raise bioavailability significantly so that it can be used as an effective radionuclide decorporation agent.

In the past three-plus years, Jay and researchers in his lab have solved the bioavailability problem. Their solution was to develop a DTPA prodrug—a drug that is not active when administered but becomes active after it enters the body. One of these prodrugs has shown 100 percent bioavailability in rats.

“We designed it so that it would have the right permeability,” Jay says. “The reason DTPA itself is not well-absorbed is because it’s very ionic, very highly charged, so it has high solubility and low permeability. We wanted high permeability and reasonable solubility, so we designed it to have this property.”

Jay is collaborating with several colleagues on the project. Russ Mumper, PhD, the John A McNeill Distinguished Professor at the School, is providing expertise in formulation and product development. Bill Zamboni, PhD, an associate professor at the School, directs the bioavailability studies. He is also director of the GLP Analytical Facility at UNC-Chapel Hill, which will conduct the bioassay work. One of Jay’s former colleagues at the University of Kentucky, Pat McNamara, PhD, is participating in the study design and pharmacokinetic analysis.

The researchers are now tackling the next hurdle: developing easy-to-administer adult and pediatric formulations for the prodrug.

“The problem is that it’s a bit of a challenging molecule to work with,” Jay says. “We want to make an oral dosage form. We initially wanted to make a solid out of it, but it is a viscous oil and we can’t crystallize it. It’s also very hydroscopic. And on top of that, it’s sensitive to water, air, and a number of things—a really uncooperative compound. Thus, we have to make formulations that deal with these issues.”

Jay also anticipates that significant taste-masking will be required for this prodrug.

Click on the links below to read about other areas of Jay's work.