Inspired by the remarkable propulsion techniques of squids, a team of researchers from MIT and Novo Nordisk has innovated a groundbreaking ingestible capsule that swiftly delivers medication directly to the stomach wall or other organs in the digestive system. This advancement has the potential to revolutionize drug delivery systems, especially for those medications that are traditionally administered through injections, such as insulin and large proteins like antibodies.
The new needle-free delivery method can also be utilized to administer RNA molecules, whether for therapeutic uses or as vaccines, targeting conditions including diabetes, obesity, and various metabolic disorders. Giovanni Traverso, the director of the Laboratory for Translational Engineering at MIT and a recognized gastroenterologist at Brigham and Women’s Hospital, articulates, “We have long sought ways to facilitate the oral delivery of macromolecules that typically necessitate injection. This development is a significant leap forward in that endeavor.”
Traverso, alongside his students and colleagues from Brigham and Women’s Hospital and Novo Nordisk, spearheaded the creation of this innovative capsule. Lead authors Graham Arrick SM ’20 and Novo Nordisk scientists Drago Sticker and Aghiad Ghazal contributed significantly to the research, reported in a recent issue of Naturehere.
Inspired by Cephalopods
The challenge of delivering large drugs orally often stems from their rapid degradation in the digestive tract. For years, Traverso’s lab has explored capsule designs that safeguard these sensitive molecules and inject them into the digestive lining without traditional needles. Traditionally, these capsules have utilized small needles or microneedles. However, in this latest study, the researchers aimed to eliminate needles altogether to minimize potential tissue damage.
Drawing inspiration from cephalopods, which propel themselves by expelling water from their bodies, the researchers fashioned two mechanisms to replicate this jetting action. They employed compressed carbon dioxide and tightly coiled springs to create the necessary force. The capsule’s carbohydrate trigger dissolves upon contact with humidity or acidic environments like that of the stomach, allowing the gas or spring to expand and eject the drug through a jet.
Through a series of experiments using digestive tract tissue, the researchers determined the necessary pressures to adequately inject drugs into the submucosal tissue, creating a localized drug reservoir from which the medication could gradually be released.
“By eliminating sharps and utilizing high-velocity jets, our system overcomes localization challenges. Unlike tiny needles requiring precise contact, our jets can deliver most doses even from a distance or slight angle,” notes Arrick.
The capsules are designed for targeted delivery, with one model featuring a flat bottom and a high dome to sit on the stomach lining and eject drugs downwards. This capsule resembles a blueberry and carries up to 80 microliters of medication. Another version is tube-shaped, designed to align itself within the esophagus or small intestine, delivering medications laterally. This variant can accommodate 200 microliters of drug.
Crafted from metal and plastic, these capsules traverse the digestive system and are excreted after fulfilling their purpose.
Advancing Needle-Free Drug Delivery
In animal studies, the capsulated system successfully delivered insulin, a GLP-1 receptor agonist similar to the diabetes medication Ozempic, and short interfering RNA (siRNA) for potential genetic disorder treatments. Notably, the drug concentrations in the subjects’ bloodstream mirrored those typically achieved through injections, while no tissue damage was observed.
Research indicates that this ingestible capsule could empower patients needing frequent insulin or injection-based medications to administer their own treatment at home, thereby enhancing ease of use and alleviating the dread associated with needles. Additionally, the elimination of sharp needle disposal offers a significant convenience. The team has also developed a variant suitable for endoscopic applications, enabling healthcare providers to directly administer drugs during procedures.
Omid Veiseh, a bioengineering professor at Rice University, comments on the research, stating, “This technology marks a substantial advancement in the oral delivery of macromolecular drugs. Previous methods often failed to achieve high bioavailability; however, the efficiency demonstrated here in animal models is promising for biologics that typically require injections.”
Looking ahead, the research team aims to refine the capsule for human testing.
This pivotal research received support from Novo Nordisk, the Natural Sciences and Engineering Research Council of Canada, the MIT Department of Mechanical Engineering, Brigham and Women’s Hospital, and the U.S. Advanced Research Projects Agency for Health.
Photo credit & article inspired by: Massachusetts Institute of Technology
