Sounding out a better way to deliver drugs?

Compared to their counterparts in the real world, physicians in the science fiction universe of Star Trek have it easy. When they need to administer a drug, they use a simple, hand-held device to shoot it through the patient's skin. No needles, no pain, no risk of infection.

Scenes like that may not be fiction for long. Low-frequency ultrasound can temporarily open up paths through usually impenetrable human skin, making it possible to introduce large, therapeutic proteins into the bloodstream, assert Robert Langer and his colleagues in the Aug. 11 Science. As a test of the technique, they successfully delivered insulin into diabetic rats and lowered the animals' blood sugar to normal concentrations.

"This could be our painless injections of the future," says Edith Mathiowitz of Brown University in Providence, R.I.

These results represent a significant advance in ultrasound-mediated drug delivery, a field that dates back more than 40 years. The barrier faced by investigators pursuing the idea has been the stratum corneum, a dense layer of dead cells that forms the outermost layer of skin. The walls of these cells consist of well-organized bilayers of fatty molecules called lipids. These lipids block all but the smallest molecules, which is why skin patches work for only a few drugs, such as nicotine.

To improve transdermal delivery, many investigators have tried using ultrasound with frequencies ranging from 1 to 3 megahertz to safely open channels through skin. Those experiments produced mixed results, and no one really understood why the technique worked when it did, says Langer of the Massachusetts Institute of Technology (MIT).

Langer, along with his MIT colleagues Samir Mitragotri and Daniel Blankschtein, recently put forward a model suggesting that ultrasound's effects on skin stem primarily from cavitation, the formation and collapse of gaseous bubbles. The bubbles come from gases, such as oxygen and carbon dioxide, dissolved in tissues, says Langer.

The key to making the technique effective, he and his colleagues thus argued, is to increase the amount of cavitation by lowering the frequency of the ultrasound to around .02 megahertz. The ultrasound-induced bubbles disrupt the stratum corneum's orderly lipid bilayers, creating "paths of minimal resistance," Langer explains.

In addition to their insulin work with rats, the researchers used the low-frequency method to deliver therapeutic doses of insulin, the immune system booster interferon-gamma, and the anemia drug erythropoietin across the skin of human cadavers, which Langer calls his field's "toughest model." Such large proteins are useless if taken orally and therefore have required injections.

The disruptions of the lipid bilayers produced by ultrasound seem to reverse quickly when treatment ends, says Langer. Though additional studies will be done to further establish safety, he hopes to start testing the technique on people within the year.