When researchers discover a new treatment for a disease, it is an exciting experience. That was certainly the case when Vasu Nair’s lab recently isolated an inhibitor that might keep human immuno- deficiency virus (HIV) from ever causing full-blown AIDS. But the experience is also a nerve-wracking one, noted Nair, a University of Georgia professor of pharmaceutical and biomedical sciences and director of the institution’s Center for Drug Discovery (CDD) located in the College of Pharmacy. “When you’re working in drug development, at any minute everything can fall apart.”

He is referring to the fact that the discovery of a potential agent for treating an ailment is only the beginning. Researchers must then conduct extensive series of tests to verify that the drug will not be toxic in humans; to demonstrate efficacy in humans, as the discovery usually involves animal models; and finally, to determine how best to deliver the drug. “There are many factors to confront,” said Svein Øie, dean of UGA’s College of Pharmacy and a professor with expertise in the area of drug disposition and delivery.

Most patients and doctors prefer drugs that can be taken orally — such treatments are convenient, painless and relatively inexpensive. But once swallowed the drug still has a long way to go. “It will have to cross membranes, be absorbed by the walls of the gastrointestinal tract and remain active in the bloodstream long enough to have an effect,” said Øie (pronounced oo-yay). “If these things don’t happen, you might as well not take the medicine at all.”

For example, the human body will completely eliminate penicillin within an hour. “This is actually not a problem for penicillin, as we can safely take very high doses to compensate for the short duration of its presence in the body,” Øie said. “But when the challenge is one of extended duration — such as the life-long issues associated with HIV infections — the treatment has to change to fit the problem.”

“Antiviral agents, such as the inhibitor that my lab is working with, need to stay in the system for many hours in order to be effective,” said Nair. Further, these treatments are frequently toxic when administered at high dosages, so additional steps must be taken to “spread out” the absorption process once the drug is administered.

One common way to do this is by placing the drug in a “micelle,” basically an empty conglomeration of molecules that can be “filled” with a pharmaceutical treatment and injected at relatively infrequent intervals. As the body breaks down the micelle, the drug inside slowly leaches out, resulting in an extended treatment.

Because different drugs require different modes of delivery — few of which are immediately obvious — the process for finding them can be arduous and frustrating. “This is one reason why this process is so exciting and scary at the same time,” said Nair. “First you are way up there, but then it can all go down when it seems like there is no safe route for delivering a drug or you find out that the body will destroy it before it has a chance to work.”

“That’s why we’re so fortunate to have the CDD here at UGA,” said Øie. “It boasts some of the very best researchers in all aspects of drug discovery — from conception to delivery — working as a team to develop treatments that do work.”

For more information on UGA’s Center for Drug Discovery, access http://www.uga.edu/cdd.

-CV