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Inspired by the jets of water that squids use to propel themselves through the ocean, a team developed an ingestible capsule that releases a burst of drugs directly into the lining of the stomach or other organs of the digestive tract.
Motivated by the way squids utilize jets to move through water and release ink, a group of researchers from MIT and Novo Nordisk has created an ingestible capsule that delivers a surge of medication straight into the stomach lining or various organs within the digestive system.
This innovative capsule could provide a new method for administering medications that typically require injections, like insulin and large proteins such as antibodies. This needle-free approach might also be utilized for delivering RNA, whether as part of a vaccine or as a therapeutic agent for treating diabetes, obesity, and other metabolic conditions.
“One of the persistent challenges we’ve been tackling is creating systems that allow for the oral delivery of macromolecules normally needing injections for administration. This achievement marks a significant step forward in that journey,” explains Giovanni Traverso, who leads the Laboratory for Translational Engineering, is an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and a senior author of the study.
Along with his students at MIT, Traverso partnered with Brigham and Women’s Hospital researchers and Novo Nordisk to develop this new capsule. Graham Arrick SM ’20 and Novo Nordisk scientists Drago Sticker and Aghiad Ghazal are the principal authors of a paper published today in Nature.
Inspired by Cephalopods
Medications composed of large proteins or RNA are usually unsuitable for oral intake since they are easily degraded in the digestive system. For several years, Traverso’s lab has been investigating methods to orally deliver these drugs by encasing them in small devices that protect them from breakdown, subsequently injecting them directly into the walls of the digestive tract.
Most existing capsules utilize a small needle or microneedles to administer drugs once inside the digestive system. However, in this current study, Traverso and his team aimed to find ways to introduce these molecules without any needles, thereby lessening the risk of damaging tissue.
To realize this concept, they drew inspiration from cephalopods. Squids and octopuses can navigate by filling their bodies with water and then forcefully expelling it through their siphon. By adjusting the water expulsion force and the direction of the siphon, these animals can control their movement and speed. The siphon organ is also capable of discharging jets of ink, which can create distractions for potential predators.
The researchers devised two methods to imitate this jetting effect, utilizing compressed carbon dioxide or tightly wound springs to produce the force necessary to eject liquid drugs from the capsule. The gas or spring remains compressed by a carbohydrate trigger designed to dissolve when in contact with moisture or an acidic setting, like the stomach. Once the trigger dissolves, the gas or spring expands, thrusting a jet of medication from the capsule.
Through a series of experiments using digestive tract tissue, the researchers determined the pressures required to expel the drugs forcefully enough to penetrate the submucosal layer, creating a reservoir that would release the drugs into the surrounding tissue.
“Beyond the removal of sharp objects, high-velocity jets also hold the advantage of being less sensitive to positioning. Unlike a small needle that needs direct contact with the tissue, our experiments indicate that a jet can deliver most of the dose from a distance or at a slight angle,” Arrick remarks.
Moreover, the team designed the capsules to target various sections of the digestive tract. One version, characterized by a flat base and a high dome, can rest on a surface like the stomach lining and aim to eject the drug downwards into the tissue. Inspired by previous work from Traverso’s lab on self-orienting capsules, this model is roughly the size of a blueberry and can hold 80 microliters of medication.
The second version features a tubular design, allowing it to align within elongated organs such as the esophagus or small intestine. In this setup, the drug is projected towards the side wall instead of downwards, with this variant capable of delivering 200 microliters of medication.
Constructed from metal and plastic, the capsules are designed to traverse the digestive system and be expelled after releasing their medicated contents.
Needle-Free Drug Delivery
In animal testing, the researchers demonstrated the ability to utilize these capsules for delivering insulin, a GLP-1 receptor agonist like the diabetes medication Ozempic, and a type of RNA known as short interfering RNA (siRNA). This RNA variant can silence genes, making it potentially viable for treating various genetic conditions.
They found that the levels of the drugs in the animals’ bloodstreams were comparable to those achieved with traditional syringe injections.
The team envisions that the ingestible capsule could be a handy option for patients needing regular insulin or other injectable medications. Not only would it simplify drug administration—especially for those averse to needles—but it also negates the necessity for handling sharp needles. They have also designed and tested a variant of the device that connects to an endoscope, permitting its use in endoscopy or surgery to administer drugs to patients.
No tissue damage was observed from the drug release, and the researchers intend to further refine the capsules with the hope of conducting human trials in the future.
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