Controlling a pill as it moves through a patient’s body could let doctors deliver drugs to precisely the right location—for instance, a tumor in the colon.
Researchers at Brown University have demonstrated a way to safely control a maneuverable pill and watch as it passes through the gastrointestinal tract.
Aside from looking for traces in a patient’s bloodstream, it is hard for doctors to tell if a drug has been delivered properly. “You can take X-rays [of tagged pills], but you can never really know what time the drug was released,” says Edith Mathiowitz, an associate professor of medical science and engineering at Brown University and principal investigator on the project. Mathiowitz’s team, which focuses on creating better drug-delivery technologies, originally built a magnetic tracking system to observe pills as they pass through the body. But the researchers soon realized they could control the pills as well.
“What we developed could be extremely useful for improving bioavailability for drugs that have even narrow therapeutic windows,” says Mathiowitz, referring to drugs that are absorbed only in specific regions of the gastrointestinal tract. “You can use it in two ways: a retention system for the stomach [to ensure the patient receives the desired dosage] and for localization in specific regions of the gastrointestinal tract—regions that are very hard to reach.”
In experiments, Mathiowitz’s team moved pills through the stomachs and intestines of rats. They developed a system to measure and control the force between a one-millimeter-long magnet within the pill and a large external magnet used to control its movement. The system automatically moves the external magnet closer to or farther from the pill’s magnet to maintain the minimum amount of force that will manipulate the pill, avoiding harm to the animal’s intestine or stomach.
Other researcher groups have shown that capsules can be manipulated inside the body magnetically, but they have not focused on minimizing the force used, explains Bryan Laulicht, first author of the research paper describing the work, published today in the online edition of the journal Proceedings of the National Academy of Sciences. “The prevailing thought was to use as much force as possible,” he says. “Our real push was to emphasize the safety.”
The pill developed at Brown is about the same size and shape as a Tylenol capsule and contains a magnet and a reservoir to hold drugs and microscopic iron particles, which show up on the X-ray.
In the animal experiments, the controlling magnet was placed next to the rat, along with a device to measure the force between the two magnets—a small cantilever that bends in response to force and is sensitive enough to detect just .01 gram of mass. The changes in the cantilever beam were fed into a computer 10 times a second, and the controlling magnet moved automatically in response. The team inferred the minimum force needed from calculations of the normal pressures that occur during digestion and was able to keep the magnetic pill in the rat’s small intestines for 12 hours. The team used an X-ray machine to track the pill in the rat.
“I think this is a good way for a more controlled drug-delivery system,” says Frank Volke, head of a research team at the Fraunhofer Institute for Biomedical Engineering in ankt Ingbert, Germany that is developing similar technology. Volke’s group created a pill containing a camera that can be controlled magnetically, and his group hopes to develop a drug-delivery system too. Other experimental approaches to controlling the movement of pills include using tiny robotic feet and using modules that self-assemble inside the body.
Slow-release pills, coated with a chemical that controls the rate at which the drug is dispensed, have been around for a while, but a way to steer a pill “would add more flexibility to that type of medication,” says Maysam Ghovanloo, an assistant professor at the Georgia Institute of Technology, who is developing a smart pill that monitors drug compliance. He suggests that monitoring magnetic fields, rather than using X-ray, might ultimately make it safer to monitor the pill’s position. Laulicht says they plan to eventually transition to a magnetic tracking system.
Moses Goddard, a general surgeon and associate professor at Brown University who was not involved in the work, says it is “an intriguing refinement of tools for improving magnetic guidance techniques.” While there are no FDA-approved magnetic guidance technologies for use with drugs, Goddard says that such an approach could help treat diseases ranging from diabetes to Crohn’s disease. The magnetic study will “give us a much better handle on how to use and manipulate magnetic forces safely and effectively in order to guide pills to areas of the bowel where we want them to go and remain for a controllable period of time,” says Goddard. “It will be particularly useful for figuring out how to guide relatively large pills to specific areas of interest.”
Metin Sitti, associate professor of engineering at Carnegie Mellon University who works on robotic pills, says the research “is very promising in the sense of medical applications of untethered magnetic capsules.”
It will take some time before such a technology will be safe to use in people. What’s more, diet and external surroundings would need to be carefully controlled to make sure that no unexpected magnetic forces come into play. But Laulicht says the system could potentially recognize whether another magnet was changing the force applied to a pill, and even counter it. “Ultimately, I do think this could be used in an outpatient setting,” he says.
If the device is eventually adapted and approved for human use, it would probably be used only in extreme cases, such as gastrointestinal cancer or inflammatory bowel disease for which other therapies have failed, says Laulicht. The team’s next steps are to try using it with real drugs, and to test it in larger animals.
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