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Perfect Timing

If this field is now poised for takeoff, it’s partly as the result of work going back a couple of decades. In the 1970s, MIT biomedical engineer Robert Langer worked out ways to build pills out of special polymers that dissolved at predictable rates to control drug dosages. Then, in 1993, Langer’s thinking on drug delivery leaped into the Information Age. “I was watching this TV show, and they were showing how computer chips are made, and I thought, boy, this would be a really neat way of making a drug-delivery system.” Langer buttonholed MIT material scientist Michael Cima and they set to work.

Their goal was to create an implantable microchip that could hold several years’ worth of medications, a miniature pharmacy that would dispense each dose automatically on schedule, freeing patients from complicated regimens. Five years later, Cima’s lab came up with a dime-sized silicon chip containing 34 drug reservoirs, each covered by a thin gold cap. Applying a small voltage to a given cap causes it to dissolve and release the reservoir’s contents.

The beauty of the device lies in its capacity to deliver drugs in a way that closely mimics how the body naturally produces chemicals-some in a steady stream, others in pulses. By carefully timing the voltage applied to each reservoir, the researchers could create different patterns of drug release. The chip could also hold many different kinds of drugs-a system that, conceptually, would work well for AIDS patients who must take 12 to 40 pills a day, at very specific intervals.

Last year, Cima and his colleagues successfully tested their system in animals. They implanted the chip in the back of a rabbit’s eye to simulate a treatment replacing the frequent eye injections required to combat vision loss from diabetes or macular degeneration. In the rabbit study, the researchers found that not only were they able to control the release of the drug, but the device itself didn’t cause any significant inflammation to the surrounding tissue.

Although this miniature pharmacy is promising, it still isn’t ready to run independently. The voltage on each reservoir must be controlled by an external power source connected to the chip via wires threaded through the animal’s tissue. Eventually, Cima hopes to make the entire system implantable by adding a tiny battery and a preprogrammed microprocessor. This will be the easiest part of the project, says Cima, who hopes to have a completely self-contained device ready for testing by the end of this year.

While the device is still under development, one of Langer and Cima’s former graduate students, John Santini, is gearing up to bring it to market. Encouraged by early lab successes, Santini founded Cambridge, MA-based MicroCHIPS in February 1999. The company has made its own improvements in the chip’s design, including squeezing up to 100 drug reservoirs onto some versions. Since each reservoir can hold only minute amounts of either powder or fluid, the company is focusing on using the chips for delivering potent drugs such as pain medications, anticancer agents, hormones and steroids. MicroCHIPS has also signed a deal with an undisclosed pharmaceutical company to develop chips carrying its proprietary drug; Santini hopes to have those chips ready for human trials in four to five years.

“People are finally starting to believe that microchip technology can be applied to drug delivery,” enthuses Santini. “Now we can take this technology and go in 50 different directions.” One possible direction: completely biodegradable polymer chips. Or a radio-controlled chip that would allow a doctor to reprogram the device remotely after implantation, should the patient need a new dosing schedule.

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Tagged: Biomedicine

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