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 non-degradable 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 during a number of days, weeks or, potentially, months, following a single administration.
The polymer is pH-responsive: it is stable in the acidic stomach environment but dissolves in the small intestine’s near-neutral pH, permitting 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.
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 (1.5–2cm in diameter), which allows gastric contents to pass into the small intestine. However, because the most convenient path to deliver these devices is through the oesophagus, which is only marginally wider than the pylorus, the researchers were interested in developing a polymer with elastic properties.
‘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,’ noted the researchers. To create this new material, they synthesised an elastic polymer and combined it in solution with a clinically utilised 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 non-toxic, 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 mould. These elastic devices had a diameter of 3cm — 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 oesophagus 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 pass safely.
The combined enteric and elastic properties of this polymer gel could significantly improve the design and adoption of gastric-resident devices. Devices that could incorporate this material include bariatric devices for the treatment of obesity, which control how hungry or full a person feels; ingestible electronics, which can diagnose and monitor a variety of conditions in the GI tract; or extended-release drug-delivery systems that could last for weeks or months after a single administration.
Such single-administration events could improve medication adherence, which remains a major clinical barrier. According to the World Health Organisation, patient adherence to long-term therapies for chronic illnesses is only 50% in developed countries, with lower rates of adherence in developing nations. Medication non-adherence costs the US an estimated US$100bn every year, the bulk of which comes from unnecessary hospitalisations. The researchers also say that single-administration delivery systems for the radical treatment of malaria and other infections could significantly benefit from these technologies.