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.
Safely stretching
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.
Read more: New material opens possibilities for super-long-acting pills
The Latest on: Long-acting pills
[google_news title=”” keyword=”long-acting pills” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Long-acting pills
- Drugs and alcohol are keeping our courts busyon May 3, 2024 at 12:51 am
A trawl through the archives of the Western People over the past 140 years will reveal that alcohol misuse has kept the courts very busy. Picture: Sean Sexton/ Some time back, a Mayoman living in ...
- Novo Nordisk (NVO) Q1 Earnings Beat, GLP-1 Drugs Boost Saleson May 2, 2024 at 2:22 am
In Diabetes Care, fast-acting insulin, Fiasp’s revenues were up 11%. NovoRapid revenues increased 1% and Human insulin revenues declined 15%. Premix insulin (Ryzodeg and NovoMix) revenues increased 12 ...
- COVID aside, vaccines and asthma drugs deliver strong quarter for GSKon May 1, 2024 at 1:08 pm
GSK said in the first quarter of 2024, the sales of Specialty Medicines increased, driven by strong HIV and Oncology performances. However, despite increased patient demand, the company noted, ...
- GSK Sees Strong Demand For Vaccines and Asthma Drugs, Raises Annual Outlookon May 1, 2024 at 6:42 am
Citing GSK CEO Emma Walmsley, the Financial Times noted, “Welcoming positive late-stage trials for gonorrhea, long-acting HIV and cancer drugs, the company had “strengthened prospects for growth in ...
- GLP-1s Are Flipping the Script, Says Doug Long | 2024 Asembiaon April 30, 2024 at 9:16 pm
The growth in spending on the glucagon-like peptide 1 (GLP-1) agonists is a “mega tsunami,” said Doug Long, MBA, vice president industry relations for IQVIA. The script that specialty drugs are the ...
- Anne Hathaway Thought She Would Never Work Again After Doing ‘Love & Other Drugs’on April 30, 2024 at 6:44 pm
Anne Hathaway once opened up about the brief but intense panic she had waiting for work after doing the movie ‘Love & Other Drugs’.
- Drug dealers rumbled with £80k cash and 2kg of cocaine after acting 'suspiciously' on Ormesby Bankon April 30, 2024 at 5:18 pm
Anthony Bennett, Shaun Wood and Jamie Hines have been sentenced at Teesside Crown Court for class A drugs offences ...
- Louisiana House committee passes new abortion pill restrictions, punts on rape exceptionson April 30, 2024 at 1:00 pm
The House Committee on Administration of Criminal Justice on Tuesday pushed back votes on several bills that would have added exceptions to Louisiana’s near-total abortion ban and advanced a measure ...
- Despite decline in contraceptive prescriptions, pill remains most popularon April 29, 2024 at 4:10 am
While the total number of contraceptive prescriptions in the UK has decreased, the pill remains the most commonly prescribed method, new data has shown.
- MSM Would Prefer Injectable, Long-Acting PrEP Over Daily Pillon April 25, 2024 at 9:14 am
Men who have sex with men (MSM) who are HIV-negative reported interest in an injectable pre-exposure prophylaxis (PrEP) that lasted longer than the daily pill, regardless of cost or coverage.
via Bing News