Puf n’ Stuf

The incidence of asthma in the United States, according to some estimates, has jumped by 50 percent since 1990. Fatalities attributable to acute airway shutdown have doubled since the late '70s, and continue to rise. Such is the immediate inspiration for David Edwards' recent research. "The main therapy for asthma is bronchodilators, administered by inhaling an aerosol mist," Edwards says. "The problem is, not much medicine gets to the lungs." Conventional aerosols wind up mostly in the mouth and throat, and from there they get into the bloodstream, resulting in negative side effects like increased heart rate. What medicine does get into the lungs can be quickly cleared away by the body's first-line defenses: large cells called macrophages whose job is to engulf and digest invaders.

David A. Edwards

As a result, bronchodilators have to be inhaled frequently and in large doses, which is troublesome since chronic use tends to dull their effectiveness and increase the risk that a severe asthmatic attack will be fatal.

Researchers are currently investigating alternatives for treating asthma. New drugs are being tested, and the search is underway for an asthma gene. Edwards, Penn State associate professor of chemical engineering, has taken a different approach. Working with Robert Langer of M.I.T. and an international team of collaborators, he has developed a new type of aerosol particle, one designed to deliver existing medications more effectively.

The standard aerosol particle, Edwards explains, is a tiny, dense sphere, one to three microns in diameter. "These small particles tend to aggregate, which means they're inefficient. They're also hard to manufacture."

What he and his colleagues have devised instead is a particle on the order of 10 to 15 microns. Magnified, this new particle looks something like a whiffle ball: spheroid, or nearly so, and riddled with holes.

"No one believed it was possible to inhale such big particles," Edwards says. By making them porous, however, the designers made them light: up to 90 percent lighter than standard particles. This means that despite their relatively large size, they weigh approximately the same as standard inhalation particles. This combination of size and airiness actually helps the new particles to penetrate more efficiently into the lungs. "They fly better," Edwards says simply. And since they are too big for scavenging macrophages to easily swallow, they can remain in the lungs releasing medication for much longer periods of time.

The potential for these new particles, Edwards says, extends well beyond their efficiency at delivering bronchodilators. In the June 20, 1997 issue of the journal Science, he and his co-authors reported that large porous particles of diabetic insulin stayed active in rats' lungs for 96 hours, 15 times longer than the longest-acting aerosol currently known. They also found that porous particles embedded with testosterone effectively raised blood hormone levels for extended periods.

"Non-invasive drug delivery is a becoming a very hot area," Edwards says, "and inhalation therapy is the mode of choice." Inhaled medications, he notes, can enter the blood stream directly through the lung walls, like oxygen. Bypassing the stomach and other organs, they cause fewer side effects than drugs taken orally, therefore requiring smaller doses. The new aerosols, he says, in addition to their usefulness against asthma, should improve treatment of cystic fibrosis and other lung disorders. Along with sparing a diabetic the daily needle, they could also be used to administer the cancer-fighting compound interferon.

Edwards and his colleagues have filed for several patents on their large-particle idea. Substantial international publicity greeted their paper in Science, sparking negotiations with several pharmaceutical companies interested in funding clinical trials. Meanwhile, Edwards reports, he is currently looking into yet another possible application: aerosol delivery of the hormone replacement estradiol, frequently prescribed for post-menopausal women to counteract bone deterioration. "Taken orally," he says, "you need big doses for estradiol to be effective," and possible side effects include an increased risk of breast cancer. "One alternative is a transdermal patch, but this may be inconvenient for a patient, and you can't co-deliver progesterone this way." (The two hormones are often used in tandem.) Edwards has tested an aerosol version in the lab, using large porous particles, and seen encouraging results. "A lower dose is required," he says, "and you get more even distribution and longer lasting effect." Several years from now, he suggests, once this innovation is refined and approved for human use, "Women who need estradiol, instead of taking multiple pills a day, might have to breathe it in only once or twice a week."

David A. Edwards, Ph.D., is associate professor of chemical engineering, 204 Fenske Lab, University Park, PA 16802; 814-863-4645; dxe11@psu.edu. In 1996, Edwards was one of five Penn State faculty members to receive a Faculty Early Career Development (CAREER) grant from the National Science Foundation. Reported by Barbara Hale of Penn State's Public Information Office.

Last Updated May 01, 1998