It can be swallowed, injected, inhaled or delivered to the bloodstream through a time-release implant. Now scientists say they have devised a new way to give patients their medicine: through a fingertip-size microchip embedded in the body that doctors can control remotely via a wireless connection.
The drug chip, more than a dozen years in the making, was used to deliver bone-strengthening hormones to women with advanced osteoporosis who otherwise would have needed daily injections. After four months, the chips were safely removed from the patients' bodies, scientists reported Thursday at a meeting in Vancouver of the American Assn. for the Advancement of Science.
"This is the kind of thing you see in 'Star Trek,' " said Robert Langer, a professor of chemical engineering at MIT and senior author of the study, which was also published online Thursday by the journal Science Translational Medicine.
Like pacemakers, defibrillators and other implantable electronic devices, the chips are controlled by radio waves in a dedicated medical frequency band. But instead of delivering an electric signal to the body, they deliver a chemical signal.
The technology could be ideal for treating conditions that require regular pulses of medication, including pain, infertility, multiple sclerosis and perhaps even diabetes. In addition to eliminating the need for needles, the chips would make it much easier for patients to comply with complicated drug regimens, doctors said.
Langer and MIT colleagues first presented the idea for a drug-delivery microchip in a 1999 article in the journal Nature. At the time, they envisioned a device that could hold small doses of potent medications in tiny compartments, each sealed by a thin metal membrane. By applying an electric charge to the membrane, it would dissolve and release the contents of the reservoir.
The researchers started a company, MicroChips Inc. of Waltham, Mass., to turn their concept into a product. Their first focus for drug delivery was women with advanced osteoporosis because human parathyroid hormone, which is used to stimulate bone formation, is delivered in doses small enough to fit on the chips and must be administered in daily pulses.
The scientists encountered a host of technological hurdles along the way, said lead author Robert Farra, president and chief operating officer of MicroChips. Major challenges included figuring out how to seal the compartments tightly and how to open the chambers at the appropriate time, he said.
Eventually, the team produced a device measuring approximately 1 by 2 inches. Inside are two microchips, each containing 10 chambers with doses of human parathyroid hormone.
They implanted the devices in eight women in Denmark, positioning the chips beneath the skin near the waistline and programming them to release daily doses of the hormone. One of devices didn't release the drug and the woman was dropped from the study. In the rest, the treatment was shown to be safe.
One concern was that the fibrous coating that typically grows around implanted devices would block the drug and prevent it from working. But the microchip-released doses behaved similarly to standard injected doses, and blood tests showed that bone formation increased. Patients reported that they were not bothered by the devices once they were implanted. The medicine itself was delivered painlessly.
As many as 70% of patients who are prescribed hormone therapy for osteoporosis don't comply with the dosing directions, which involve daily injections for up to two years, experts say.
"The major advantage of the chip is that the patient takes every dose that is prescribed," said Dr. Robert Neer, a study coauthor and director of the Massachusetts General Hospital Bone Density Center in Boston. "The chip is more reliable than the patient."
Mark Saltzman, a biomedical engineering professor at Yale University who was not involved in this research, said the advance solved an intractable problem in implantable drug delivery: how to administer medications in pulses rather than at a constant rate. Some medications, including the hormone the osteoporosis patients were taking, aren't effective unless they're given in discrete doses, he said.
Eventually, drug-dispensing chips could be used to deliver any drug — or combination of drugs — that is potent enough to be administered in the tiny doses the device can store, Langer said.
The microchips wouldn't have the capacity to store the amount of insulin that patients with diabetes must inject each day to regulate their blood sugar. But the chips could be built with glucose sensors that would notice when a patient's blood sugar plunged too low and respond by triggering a release of glucagon, a hormone that raises blood sugar levels.
Microchips could theoretically be used to deliver a wide array of medicines, but they would be practical only for drugs that treat serious illnesses, Langer said.
"If someone had a really bad disease like cancer, then sure — the type of procedure you're willing to go through is more drastic," he said. But if you have a cold, he added, you'd probably still just take a pill.
Farra said it would take at least another four years to get an osteoporosis drug approved for the marketplace. In the meantime, he said, MicroChips will focus on building a chip with 365 wells, to accommodate a year's worth of daily doses.