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Inner-space Invaders:
Tinkering with the Very Tiny

by Jeff Worley

In the battle against cancer and other devastating diseases, pharmaceutical companies are developing new drugs every day. Many of these drugs work fine in cell culture tests but then fail the crucial water test.

Illustration of nanoparticleAround 40 percent of all newly discovered compounds have poor water solubility or none at all. This is a problem because the human body is a huge reservoir of water—we're two-thirds water. "Lots of drugs get killed along the developmental pipeline because they can't be formulated to be used in the body," Jay says.

So here's the research challenge: How do you increase the water solubility of a drug that doesn't want to dissolve in water?

Photo of Russell Mumper and Mike JayRussell Mumper (left) and Mike Jay have collaborated on various research projects since the early '90s, when Mumper was a graduate student and Jay his advisor.

"In order for a drug to be injectable or to be absorbed from the stomach, it has to show some water solubility," says Jay. "One way to do this is to fake it—put the drug into an environment in which it is soluble, an oil droplet, for instance, and send it into the body this way." This idea is at the heart of the researchers' new patented process, which they term "nanotemplate engineering."

"The drugs that we would like to formulate are not very water soluble, but they are soluble in oil," Mumper says. These miniscule spheres—under an electron microscope they look like a cluster of marbles—can be engineered to seek out a particular tissue or cell in the body. After the drug reaches its target, a cancer cell, let's say, the drug is welcomed in and is released from the particles. It then leaches out into the cell, killing it.

But everybody knows water and oil don't mix. So how do these designer particles manage to pass through water to find their designated target? The answer, Jay says, has to do not only with size but also with chemicals called surfactants.

"To make oil and water mix, we resort to a bit of scientific trickery," Jay says with a hint of a smile. "A surfactant is a surface-active agent—hand soap is a good example. In our case, it's something that will align at the interface between oil and water."

The surfactant they add to their mix, he explains, has an oil-friendly part that extends into the droplet and a water-friendly part that lies on the surface of the droplet, virtually surrounding it. The surfactant serves as a kind of mediator. It's what permits, in large part, the unlikely marriage of water and oil. The purpose of the surfactant is to stabilize the oil droplet, to keep it well suspended.

"These microemulsions are stable," Mumper says. "They won't separate over time, like oil and vinegar will, for example, and this stability is exactly what we want." He adds that he and Jay have carefully chosen an oil that is a liquid at slightly elevated temperatures (120º F or so), but at room temperature is a solid. "When we cool the mixture back to room temperature, the droplets transform into tiny, solid particles. [Substances that can change form are fairly common—think of water and ice.] They have the drug inside them, and they're still coated with the surfactant."

Illustration of nanoparticleThe researchers' nanoparticle tinkering doesn't stop here. "By using 'recognition molecules' attached to the surface of the particles, we can direct them to specific parts of the body, say, a receptor on a tumor," Jay explains. Nanoparticles can be easily injected or can be dried and incorporated into a tablet, he explains. "The particles head for the cancer cell and bind to a receptor. What we hope will happen then is that the cancer cell will engulf the particle and, in doing so, engulf the drug that will leach out into the cell."

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