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Past Winner
2008 E.W.R. Steacie Memorial Fellowship

Jean-Christophe Leroux

Pharmaceutical Chemistry

Université de Montréal

Jean-Christophe Leroux
Jean-Christophe Leroux

For pharmaceutical chemist Jean-Christophe Leroux, the future of administering drugs lies in the ability to send the smallest amount of medication to precisely the right spot in the body in order to do its therapeutic work. It’s the pharmaceutical equivalent of keyhole surgery, achieving maximum benefit while causing the fewest side effects.

Full realization of that goal is many years away, but Dr. Leroux has made significant inroads through his innovative work in designing molecules that can travel through the body on their way to disease sites. His 2008 NSERC E.W.R. Steacie Memorial Fellowship will help him bring that research closer to fruition.

More drugs are available today than ever before, but their effectiveness can be limited by factors that include poor solubility in water, the inability to cross biological barriers such as cell membranes, and the lack of a means to deliver them specifically to the disease site. Some also have varying degrees of toxicity, so care must be taken not to overexpose patients.

That’s where drug delivery specialists like Dr. Leroux come in. Essentially, he and his colleagues design molecules that the body will recognize and bring to a specific type of cell. The required drug is attached to that molecule and piggybacks its way to the place where it is needed.

“Most delivery systems rely on the same principle,” he says. “What changes is the type of carrier that we use to transport the drug.”

Targeted delivery has been around for about 30 years. Thanks in part to developments in nanotechnology, though, the level of research and the sophistication of the delivery has increased dramatically in the last decade. Still, creating new systems involves far more than simply attaching a drug to a promising molecule and wishing it “bon voyage.” “There are several parameters that you have to control,” explains Dr. Leroux. “By playing with the size, shape and surface properties, you change the way the system will behave once it is injected.”

The first challenge involves particles being able to make it past the body’s immune system with their payload of drugs. A special coating is needed to perform that job, preventing the particle from setting off any alarms before it reaches its destination and attaches, for example, to the site of a tumour.

After the particle passes through blood vessel walls, cells walls and other obstacles, the next big hurdle involves releasing the drug. “The release rate at the target is very important and very difficult to control,” emphasizes Dr. Leroux. If the drug is released too quickly or too slowly, too early or too late, it will not be effective. At the most basic level, a particle can be designed to simply biodegrade after a certain time in order to release the drug. The more “intelligent” the system, however, the more likely it is to distribute the drug effectively.

One of the options is to design a carrier that reacts to a change in conditions found only in the right part of the body, such as a certain level of acidity. An external stimulus, such as light, could also trigger the release of the drug.

In essence, the idea is to mimic the evolutionary tricks of organisms such as viruses. “Viruses are very efficient delivery systems,” he says. “They can travel in the body, and when they have reached the right cell they can deliver their genetic material to do what they have to do to replicate.”

More efficient delivery has big potential payoffs. Side effects of medication, for example, can be significantly reduced. One study conducted by his group found that three times the amount of an anti-cancer drug could be delivered through targeted delivery before causing the same side effects as conventional delivery.

Although he is exploring a variety of possibilities, much of Dr. Leroux’s interest is centred on polymeric micelles, tiny structures that effectively form a closed capsule that can carry drugs to their target. He is also working on using lipids, molecules which are soluble in fat, to transport drugs. His lab has tested these new systems extensively in cells, and has begun tests in animals.

Another possibility, one that conjures up images from science fiction novels, involves a collaboration with Sylvain Martel, the Director of the NanoRobotics Laboratory at École Polytechnique de Montréal. They’re trying to develop a system based on nanoparticles that can be controlled with an MRI machine. “This is a very exciting project because you will be able, in real time, to locate where the particles are in the body and to change their trajectory,” he says.

Dr. Leroux’s role is the design of the nanoparticles, which in addition to meeting all the usual requirements must also respond to magnetic forces. Then, once they release the drugs they are carrying, they have to quietly biodegrade and be eliminated from the body.

Over the next few years, he expects to see a lot more progress on various new drug transport systems, including starting clinical trials in humans. “The ideal situation would be to have a platform technique that would work for all sorts of drugs,” he concludes. “We’re always trying to develop materials with this in mind. However, most of the time we need to tailor a particular material to make it fit with the drug we’re going to use.”