NEW YORK (360Dx) – Researchers at the Massachusetts Institute of Technology, Draper Laboratory, and Brigham and Women’s Hospital are developing an ingestible capsule that they anticipate could one day relay diagnostic information and release drugs in response to smartphone commands.
The researchers are developing multimaterial 3D-printed capsules to sense infections, allergic reactions, or other medical conditions prior to the release of a suitable drug to treat the condition. Thus far, they have tested the ingestible sensors in the gastrointestinal tracts of pigs.
"Our goal is to develop systems in the future that enable closed-loop care, where we deploy a specific drug and can adjust its dose based on that parameter that we're monitoring," Giovanni Traverso, a visiting scientist in MIT’s Department of Mechanical Engineering, said in an interview. The developers anticipate that they can begin testing ingestible sensors in human patients in about two years.
Traverso — who is also an assistant professor at Harvard Medical School and a gastroenterologist at Brigham and Women's Hospital — recently published a paper with colleagues in the journal Advanced Materials Technologies describing the development of the capsules and their performance in pigs.
In the study, the researchers showed that the capsules remain in the gastric cavity for 36 days and communicate wirelessly, using Bluetooth, for 15 days. Most long-term resident electronics devices require invasive procedures for implantation as well as a specialized receiver for communication, they noted.
The new system "houses a set of electronics that can communicate externally using signals that represent different parameters in the body," Traverso said. "The signal in our proof-of-concept device is temperature. We also showed that we can include other components in the system, such as microchambers to trigger the release of a drug."
The devices could be designed to communicate with other wearable and implantable medical devices to contribute information that could be communicated to a patient’s or doctor’s smartphone, he said.
This technology development is noteworthy because it demonstrates the ability for capsules to reside within the stomach for comparatively long periods and be remotely triggered, Christopher Bettinger, an associate professor of materials science and biomedical engineering, at Carnegie Mellon University, said in an interview.
In July, Bettinger, who is not affiliated with Traverso's team, published a review of advances in materials and structures for ingestible electromechanical devices in the journal Angewandte Chemie in July.
He told 360Dx that 3D printing of these devices could be an aid in the manufacturing of patient-specific ingestible electronics devices. "Edible electronic devices for drug delivery may also benefit from advances in materials such as biocompatible batteries or flexible biodegradable elastomers, he said.
The technology being developed by Traverso and his colleagues along with broader development of ingestible electronics "have the potential to improve the delivery and patience compliance of oral medications," Bettinger added.
For the past several years, Traverso and his colleagues have been working on a variety of ingestible sensors and drug delivery capsules, which they believe would be useful for long-term delivery of drugs that currently have to be injected.
In 2016, they built a star-shaped capsule with six arms that fold up before being encased in a smooth capsule. After being swallowed, the capsule dissolves and the arms expand, allowing the device to lodge in the stomach. The researchers have also designed sensors that can detect vital signs such as heart and breathing rate.
In their current study, funded by the Bill and Melinda Gates Foundation and the National Institutes of Health through Draper Labs, the researchers set out to combine features they had previously developed. They designed a capsule used to monitor temperature and relay it to a smartphone within arm’s length. Their new device unfolds into a Y-shape after being swallowed and remains in the stomach until it breaks into smaller pieces and passes through the digestive tract.
One of the capsule's arms includes four small compartments that can be loaded with a variety of drugs.
They 3D-printed the capsules to enable building complex compartments in the capsule and to build it from alternating layers of stiff and flexible polymers that provide protection from stomach acid.
The device is powered by a small silver oxide battery. However, the researchers are investigating whether they can replace the battery with alternative power sources, such as the wireless transfer of power from an antenna outside the body to another one inside the digestive tract, or the use of stomach acid to generate power.
If the researchers succeed in developing a platform to continuously monitor core body temperature, that function that can be important in enabling immediate interventions for people at risk of hypothermia or hyperthermia, Traverso said.
More broadly, hospital staff, who routinely measure a patient's temperature during a single day, could use the capsules, he noted.
The researchers are developing the system to monitor other vital signs such as respiratory rate and heart rate; to detect and monitor infections, which is of importance to immunosuppressed patients; and to detect a deficient supply of blood to a body part that would enable rapid medical intervention to prevent critical blood loss, Traverso added.
3D printing enabled the developers to rapidly build and test different designs of the capsule modules with many sensing and drug delivery compartments. They tested capsules made from polylactic acid and are experimenting with polyurethanes. The overall system also uses a gold membrane that could be dissolved to rapidly release a drug, Traverso said.
"Part of the continual development [of the system] involves ensuring that the materials are biocompatible," Traverso said. Biocompatibility challenges are not as much of a concern for ingestible systems that pass out of the body as for systems that are implanted and fixed, he said.
The research team is continuously testing different mixtures of materials to ensure that they are safe with the body.
He said that a commercial system that diagnoses body parameters and releases a drug to treat a medical condition could be available in three to five years, and the the research group plans to seek US Food and Drug Administration clearance. Whether the system will be commercialized in an academic setting or through a startup or industrial collaboration "remains to be seen," Traverso said.
In his Angewandte Chemie review, Bettinger said that "the increasing importance of gut health on overall well-being and the prevalence of many gastrointestinal diseases have renewed focus on this emerging class of medical devices."
Bettinger said he believes that the commercialization prospects for the technology being developed by Traverso and his colleagues "are potentially very strong."
Although there are regulatory challenges with qualifying any type of new medical device including this one, the non-invasive nature of ingestible electronic devices "could accelerate the approval process," Bettinger said.
He noted that finding the right indication and drug that could benefit from the technology is one challenge that needs solving.