A pH-responsive polymer gel could create swallowable devices, including capsules for ultra-long drug delivery
Medical devices designed to reside in the stomach have a variety of applications, including prolonged drug delivery, electronic monitoring, and weight-loss intervention. However, these devices, often created with nondegradable elastic polymers, bear an inherent risk of intestinal obstruction as a result of accidental fracture or migration. As such, they are usually designed to remain in the stomach for a limited time.
Now, researchers at MIT’s Koch Institute for Integrative Cancer Research and Massachusetts General Hospital (MGH) have created a polymer gel that overcomes this safety concern and could allow for the development of long-acting devices that reside in the stomach, including orally delivered capsules that can release drugs over a number of days, weeks, or potentially months following a single administration.
This polymer is pH-responsive: It is stable in the acidic stomach environment but dissolves in the small intestine’s near-neutral pH, allowing for safe passage through the remainder of the gastrointestinal (GI) tract. The material is also elastic, allowing for the compression and folding of devices into easily ingestible capsules — meaning this polymer can be used to create safe devices designed for extremely prolonged residence in the stomach.
“One of the issues with any device in the GI tract is that there’s the potential for an obstruction, which is a medical emergency potentially requiring surgical intervention,” says Koch Institute research affiliate Giovanni Traverso, also a gastroenterologist at MGH and an instructor at Harvard Medical School. “A material like this represents a real advance because it is both safe and stable in the stomach environment.”
Traverso and Robert Langer, the David H. Koch Institute Professor at MIT and a member of the Koch Institute, are the senior authors of a paper in the July 27 issue of Nature Materials that describes the application of this new polymer gel for creating gastric devices. Shiyi Zhang, a postdoc at the Koch Institute, is the paper’s lead author.
Designing devices for the stomach is a complicated matter of sizes and shapes. The stomach naturally empties its contents in a matter of hours, so for devices to be retained, they must be wider than the pylorus — the valve at the end of the stomach, about 1.5 to 2 centimeters in diameter, that allows gastric contents to pass into the small intestine. However, because the most convenient path to deliver these devices is through the esophagus, which is only marginally wider than the pylorus, the researchers were interested in developing a polymer with elastic properties.
“An elastic device can be folded into something small, such as a capsule, and be easily ingested through the esophagus before expanding in the stomach, restoring its original shape,” Zhang says. “When you have a device that’s larger than the pylorus, there’s a much higher probability that it will be retained longer in the stomach.”
But the size and shape of existing devices with elastic polymers have been limited by safety concerns, as there is a greater risk for fracture if a device is too large or too complex. Because of this, the researchers wanted their polymer to also be enteric — or have a mechanism that would enable it to pass through the stomach unaltered before disintegrating in the intestines.
“To lower any possible risk of obstruction, we wanted a material that could dissolve in the intestines, thereby dissociating the device, and safely pass out of the body,” Zhang says.
To create this new material, the researchers synthesized an elastic polymer and combined it in solution with a clinically utilized enteric polymer. Adding hydrochloric acid and centrifuging the solution resulted in a flexible, yet resilient, polymer gel that exhibits both elastic and enteric properties.
The researchers used the gel polycaprolactone (PCL), a nontoxic, degradable polyester, to construct several device prototypes. They first created ring-shaped devices by using the gel to link arcs of PCL in a circular mold. These elastic devices had a diameter of 3 centimeters — wider than the pylorus — before they were folded into orally ingestible capsules.
In testing the capsules in pigs, the researchers found that the rings expanded into their original shape within 15 minutes of ingestion and remained in the stomach for up to seven days. After the device passed out of the stomach, the polymer gel dissolved, allowing for the safe passage of the small PCL pieces without obstruction. The researchers also created larger devices in various shapes that could be folded and delivered through the esophagus with the assistance of an endoscope. These devices remained in the stomach for up to five days, after which the gel similarly dissolved, allowing for the remnants of the device to safely pass.
The Latest on: Long-acting pills
via Google News
The Latest on: Long-acting pills
- FDA approves first long-acting HIV medon January 26, 2021 at 10:54 am
The Food and Drug Administration has approved the first long-acting HIV medication. Cabenuva is a monthly shot that replaces daily pills to control the HIV virus from replicating, according to ...
- FDA approves HIV treatment replacing daily pills with monthly injectionson January 25, 2021 at 10:13 am
Viiv Healthcare's Cabenuva replaces a traditional daily pill regimen to treat HIV with two injections every month ...
- FDA approves first long-acting HIV drug combo, monthly shotson January 22, 2021 at 11:07 pm
U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills now used to control infection with the AIDS virus. Thursday’s approval of the two ...
- Long-acting HIV drug approvedon January 22, 2021 at 9:45 am
The Associated Press U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills now used to control infection with the AIDS virus.
- FDA approves ViiV’s Cabenuva as first complete long-acting regimen for HIV treatmenton January 21, 2021 at 11:58 pm
The U.S. Food and Drug Administration approved ViiV Healthcare's Cabenuva as the only complete long-acting regimen for the treatment of HIV-1 infection in adults.
- First long-acting HIV treatment Cabenuva approved by FDA as monthly shotson January 21, 2021 at 9:28 pm
US regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills now used to control infection with the AIDS virus. Thursday’s approval of the ...
- Janssen Announces U.S. FDA Approval of CABENUVA (rilpivirine and cabotegravir), the First Long-Acting Regimen for the Treatment of HIVon January 21, 2021 at 9:08 pm
The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) has approved CABENUVA (consisting of Janssen’s rilpivirine and ViiV Healthcare’s ...
- U.S. FDA approves GSK unit's long-acting HIV injectionon January 21, 2021 at 7:34 pm
The U.S. Food and Drug Administration on Thursday approved a long-acting HIV injection from British drugmaker GlaxoSmithKline's HIV treatment division, ViiV .
- FDA approves first long-acting shots for HIVon January 21, 2021 at 5:23 pm
U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace the daily pills people use to control infection of the AIDS virus. Thursday's approval of the two ...
- FDA approves 1st long-acting HIV drug combo, monthly shotson January 21, 2021 at 2:33 pm
U.S. regulators have approved the first long-acting drug combo for HIV, monthly shots that can replace daily pills ...
via Bing News