Beyond Needles And Pills

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A substantial portion of drugs taken orally, in pill or liquid form, is lost to digestive processes and removed by the liver, and what remains can irritate the intestinal tract. Enter transdermal patches. First designed to treat motion sickness, they slowly deliver drugs through the skin from a reservoir within the patch, and are being used increasingly to treat hypertension, angina and other disorders. So far, the patches are limited to carrying small-molecule drugs that can diffuse through the skin. But several teams are experimenting with electrical or ultrasonic devices that can also push larger-molecule drugs through the skin or create temporary macropores through which these bulky molecules can pass.

Some of the new drug-delivery solutions are elegant but decidedly low tech. "For people who have a tough time swallowing pills," says Langer, "a company called Alkermes has developed a special straw that is loaded with a premeasured dose of dry medication. The patient then uses the straw to sip water, a soft drink or apple juice." And for a toddler who spits out, throws up or gags on fever-reducing medication, there are fast-acting suppositories to which parents can resort.

At the opposite end of the technology scale, Eldrid Sequeira, a Utah State University graduate student, is designing microscopic "submarines"--drug-bearing capsules that someday could be propelled through the bloodstream by bacteria to attack disease. Looking even further ahead for alternative means of driving these tiny craft, he is considering building biomotors 100 billionths of a meter wide that would use only the bacteria's hairlike, propelling flagella to move ahead.

Equally remarkable, Langer and his colleagues reported in the journal Nature that they had engineered a prototype microchip that could someday be swallowed or implanted and work as a programmable "pharmacy." It contains up to 1,000 tiny reservoirs of chemicals that are released in the proper quantity and sequence when the chip is exposed to low voltages.

Brain tumors have long presented a major challenge to drug delivery because of the especially leakproof blood-vessel walls in the brain, which make it difficult to administer conventional chemotherapy there. Drug-bearing wafers may be one answer. After the brain surgeon removes as much of the tumor as possible, small drug wafers are inserted at the tumor sites. Over time the wafers slowly release a chemical that prevents the recurrence of new tumors. The technique seems to work. A 1997 clinical trial showed that after two years, 31% of glioblastoma patients with implanted wafers were still alive, compared with only 6% in the control group.

For all the promise of the new drug systems, M.I.T.'s Langer is still looking ahead to what many researchers hold out as an ultimate goal: a magic bullet placed in the bloodstream that "goes right to where you want it and only there, and does exactly what you want it to do and only that. We are not there yet."

But apparently we're getting closer.

--Reported by David Bjerklie/New York