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The patient leans back in his chair and closes his eyes, waiting to receive his first chemotherapy treatment for advanced colon cancer. His nurse locates the tiny catheter just beneath the skin of his chest and connects it to an IV tube. A clear fluid containing an anticancer drug travels down the tube, through the catheter and into the man’s blood vessels. The drug travels throughout his body in search of the fast-dividing cells characteristic of cancer-but only a relatively small portion of the drug will reach those cells. Instead, much of it will end up attacking hair follicles, immune system cells and tissues where noncancerous cells are dividing quickly. The treatment lasts an hour as the patient sits there, apprehensive not only about his disease but about side effects. Will he lose his hair? Will he feel nauseous? A few hours later, nausea sets in. By the next treatment, the hair loss he feared has begun.

Now fast-forward 10 years or so. Gone are the catheter and the shotgun approach. In their place is a remarkable little particle, invisible to the naked eye, that contains far more intelligence than the entire current system of drug delivery. Taken orally, the particle passes undisturbed through the stomach and small intestine and into the colon, where it homes in directly on the tumor cells. There, it releases a powerful anticancer drug that destroys just the cancerous cells-with no side effects.

Sound far-fetched? Well, it isn’t possible yet. But it could be quite soon, thanks to a new generation of “smart” delivery vehicles under development at a handful of universities and startup companies. These new methods offer the ability to precisely control the timing of a drug’s release. What’s more, they aim for laserlike targeting of just the right tissues and cells. And a little farther in the future lies the capacity to operate autonomously, gathering feedback from the body and adjusting treatment accordingly. The pioneers in this young field believe they will bring the first of these new weapons against disease into clinical trials as soon as five years from now, freeing patients from the pain and side effects of pills and injections, and also opening the door to whole new classes of treatments that aren’t possible with today’s delivery systems.

Gathering Speed

Smart drug delivery is still in its infancy-and at the same time it’s a discipline whose time has come. At the moment, most of the research is happening in academic labs, along with a few start-ups (mostly spun out of academe). But the promise of the technology is so great that it has caught the attention of large drug companies and other manufacturers. “They’re certainly poking around at conferences,” says Carl Grove, president of Columbus, OH, startup iMedd. “Even the Motorolas and the Intels, you see them nosing around too.” And though analysts have yet to offer their forecasts for the field, insiders often cite a 1998 report from the European Network of Excellence in Multi-functional Microsystems (an industry consortium funded by the European Union) predicting a worldwide market of $1 billion for microfabricated drug-delivery devices by 2002.

Much of this interest is driven by rapid progress in microfabrication. Researchers now have the ability to build devices with features small enough to interact with single cells, and even individual molecules. Getting the devices small enough is the key to their promise, says Mauro Ferrari, director of the Center for Biomedical Engineering at Ohio State University. “There are some major unsolved problems in medicine that can only be solved with micro- and nanotechnologies.”

When the delivery systems reach practicality, there’s a whole new suite of potential drugs waiting in the wings: proteins discovered as a result of the recent explosion of genomic information. But expanding the use of proteins as drugs demands much better means of delivery than are currently available, since most of these large biological molecules are either too potent to deliver through injection, or too fragile to withstand the enzymes and drastic changes in pH found in the stomach and intestines. With an entire new class of protein drugs in view, the enabling technologies in hand, and corporate interest growing, the next couple of years look like just the time for smart drug delivery to emerge as a field.

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Tagged: Biomedicine

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