If the device that Cima has built specializes in complex scheduling, other groups are focusing on precise targeting. Take Ohio’s iMedd, one of the first companies in the field. IMedd was founded in Silicon Valley to commercialize the inventions of Ohio State’s Ferrari (then a professor at the University of California, Berkeley). When Ferrari went to Ohio in 1998, the company followed; but it continues to collaborate with former graduate students from Ferrari’s Berkeley lab.One of them is Tejal Desai, now an assistant professor of bioengineering at the University of Illinois at Chicago. She and iMedd are building chiclet-shaped silicon particles so small (150 microns across and 50 microns thick) they’re invisible to the naked eye. On one side, the researchers etch from two to 20 drug-containing reservoirs, each sealed with a polymer plug. Like pills, the particles are swallowed, but unlike pills, they release drugs only at a predetermined time and location. “We want to make something that actually responds to the environment and interacts with the cells, instead of just going in and releasing a drug,” says Desai.
The targeting mechanism is a special coating deposited over the reservoir-bearing side. In initial experiments, Desai’s team is making particles aimed at delivering fragile drugs such as proteins directly to the bloodstream, so the researchers are coating the particles with a tomato protein called lectin that binds specifically to cells lining the intestine. The idea is that the particles could travel undisturbed through the harsh environment of the stomach, protected by the silicon casing. Once a particle reached the intestine, the lectin-coated side would bind to the lining. There, the system would ferry the drug quickly across the intestinal lining into the nearest blood vessel.
To get the job done, some of the reservoirs would hold chemicals to widen the spaces between the intestinal lining cells, and some would carry another chemical that blocks the enzymes that could degrade the drug. By modifying the polymer plugs covering the reservoirs, the researchers could make sure that the protective chemicals were released first. With these lines of defense in place, the drug could pass safely through the intestinal wall and into the bloodstream, and the empty particles could pass through the rest of the digestive tract.
Currently, Desai is testing the basic setup in rats. If that works out, she’ll begin adapting the particles for an array of targets. One idea is to replace the surface layer of lectin with an antibody that binds to tumor cells in the colon; that way, the particle could carry anticancer drugs directly to cancerous masses. Such a system could virtually eliminate side effects, revolutionizing treatment for the 130,000 or so patients who are diagnosed with colon and rectal cancer each year in the United States.
While Desai’s system offers great flexibility, in some cases intravenous delivery is still best. IMedd is therefore developing a polymer particle small enough for injection-just a few microns across-that will have the same targeting abilities as Desai’s prototype. “Now it gets even more complicated,” says Ferrari. “You need to make a delivery device that can perform multiple functions even at that size.” Derek Hansford, a biomedical engineer at Ohio State, is leading a project that aims to deliver just that. “The biggest challenge currently is in producing uniform particles with uniform material properties in large quantities,” says Hansford. Eventually, he plans to fill the particles with drugs and coat them with targeting agents in a system much like Desai’s.