Miniature Medicine Balls

Blood vessels, like highways and byways that reach most addresses, run through almost all the body's tissues. The problem for physicians is that drugs in this transportation network travel nearly everywhere, finding their way to many more nooks and crannies than they are meant for. Now German researchers have found a low-tech solution for getting the goods to specific bodily addresses: tiny polymer spheres bearing medicine that can be lodged in specific sets of narrow vessels called capillaries before releasing their loads. The technique, reported in next month's Nature Biotechnology, could provide a new vehicle for delivering drugs to people with heart disease and other ailments.

Heart attacks happen when clogged arteries prevent the heart from circulating enough blood to sustain itself. One possible treatment is to create new routes for blood to get to the heart muscle by using a protein called fibroblast growth factor (FGF) to stimulate new blood vessel growth. FGF, however, has not found widespread use as a treatment yet because of two key problems: Enzymes quickly deactivate circulating FGF, and high doses can dilate blood vessels and dangerously lower blood pressure.

To deliver FGF where it's needed more precisely, a team led by physiologist Wulf Ito of the Max Planck Institute for Physiological and Clinical research in Bad Nauheim, Germany, attached FGF to tiny couriers--resin spheres, 7 micrometers in diameter, that are a shade too large to squeeze through a capillary. A drug-laden sphere "looks like a golf ball with FGF in the little dents," says Ito.

The researchers tested the technique on healthy pigs, injecting the spheres into an artery that feeds a section of heart muscle. Within seconds, 60% of the spheres lodged in the capillaries fed by the artery. The remaining 40% were probably slightly smaller and squeaked through, Ito says. Not to worry, the rest of the body "gets a very, very small dose," he adds. Indeed, the remaining spheres were so diffusely distributed outside heart tissue that the researchers couldn't find a single one.

If further research shows that the injectable spheres trigger new capillary growth, they could have "immense clinical ramifications," says Elazer Edelman, director of the Harvard-MIT Biomedical Engineering Center in Cambridge, Massachusetts. Already, similar spheres are getting their first tryout in people: Edelman has been conducting tests in which FGF-bearing spheres are implanted in people's chests while they are opened up for coronary bypass surgery. "It will be intriguing to see how these injectable spheres work in clinical trials," he says.

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