Making tiny plastic particles to deliver lifesaving medicine
BALTIMORE, MD., September 29, 2003 -- Many medications such as therapeutic DNA, insulin and human growth hormone must enter the body through painful injections, but a Johns Hopkins researcher is seeking to deliver the same treatment without the sting.
Justin Hanes wants to pack the drugs inside microscopic plastic spheres that can be inhaled painlessly. Inside the lungs, the particles should dissolve harmlessly, releasing the medicine at a predetermined pace.
"We've made significant progress," said Hanes, an assistant professor in the Whiting School of Engineering's Department of Chemical and Biomolecular Engineering, "especially when you consider all of the challenges we've faced in designing and synthesizing these new biomaterials."
For one thing, the polymers used in making such particles must dissolve slowly in the body, releasing the medicine over a prescribed period of hours, days or even weeks. Also, these materials must be strong and flexible, so that the particles do not crack or crumble before delivering their treatment. At the same time, the particles must not stick together, forming clumps that will prevent proper travel through the air passages. Once the particles deposit in the lungs, some therapies will require that they cross the thick mucus lining of air passages prior to releasing their medicinal cargo. Finally, the materials must not trigger a strong immune response, in which the body's natural defense system attacks a particle before it has delivered its dose.
Hanes and his lab colleagues have overcome many of these hurdles, publishing their research results in peer-reviewed journals. Last year, in an issue of "Biomaterials," Hanes' team, including associate research scientist Jie Fu and doctoral candidate Jennifer Fiegel, reported that it had synthesized a new type of porous polymer particles capable of releasing drugs in an environment resembling the deep lungs. Importantly, the components used to create these plastic microspheres were materials already FDA-approved for other medical applications, making it more likely they will pose no health hazards to humans in their new polymeric form.
Recent work by Hanes, doctoral candidate Michelle Dawson and associate professor Denis Wirtz has focused on understanding how to alter the design of drug-carrying particles so that they can more efficiently cross the mucus lining in the lungs to reach their cell targets underneath. Reports on this work are expected appear shortly in the "Journal of Biology Chemistry," "Biotechnology Progress" and the "Journal of Aerosol Medicine."
Earlier this year, in "Proceedings of the National Academy of Sciences," Hanes, Wirtz and Junghae Suh, a doctoral candidate, reported that their nanoscopic particles appear to be able to efficiently deliver therapeutic genes by carrying DNA directly to the cell nucleus. Someday, Hanes said, this technique also may prove useful in delivering toxic cancer-fighting drugs only to cells affected by the disease.
Hanes has focused much of his attention on the lungs because they possess several advantages over other drug delivery routes. When medicine is swallowed, it must pass through the stomach, where it may be degraded by digestive acids. Injections may avoid this problem, but they also are painful and may be difficult for some patients to administer to themselves. Inhalation, however, as smokers and asthmatics know, is generally a quick and painless method of getting a drug into the body. Still, Hanes noted, "the lungs are pretty sacred ground. You have to be very conservative about what you put in there."
As a doctoral student at MIT, Hanes played a leading role in developing porous polymer drug delivery particles coated with a special surfactant native to the lung. The surfactant is designed to fool the body into thinking these particles belong in the lungs, warding off an immune response. In 1999, Hanes and his colleagues received a U.S. patent for this invention; Hanes currently holds eight U.S. patents for advanced drug delivery applications.
At Johns Hopkins, he is building upon this research by synthesizing improved inhalation particles, each about a tenth of the diameter of a human hair. He soon hopes to begin testing their safety and effectiveness in animal models and eventually in human trials. Hanes also is trying to produce even smaller particles that could be used to deliver powerful medications directly into diseased cells, while leaving normal tissue unharmed.
Justin Hanes' Web Page: www.jhu.edu/~cheme/hanes/index.html
Source: Johns Hopkins University
Posted: September 2003