Revolutionary Bioinspired Capsule Delivers Insulin and RNA Directly into the GI Tract – No Needles Required

MIT and Novo Nordisk Develop Squid-Inspired Capsule for Needle-Free Drug Delivery

In a groundbreaking innovation, researchers from MIT and Novo Nordisk have created an ingestible capsule capable of delivering drug doses directly into the walls of the stomach or digestive tract without using needles. Drawing inspiration from the unique propulsion and ink-shooting mechanisms of squids, this new technology could transform how medications like insulin and other large protein-based drugs are administered.

Traditionally, drugs composed of large molecules such as insulin, RNA, or antibodies require injections due to their inability to withstand the digestive tract's harsh environment. Giovanni Traverso, an associate professor of mechanical engineering at MIT and a senior author of this study, emphasized the significance of this advancement: “One of the longstanding challenges in medicine has been creating oral delivery systems for macromolecules that typically require injections. This work is a major step forward in that direction.”

The capsule, described in the journal Nature, is the result of collaboration among MIT, Brigham and Women’s Hospital, and Novo Nordisk. It aims to simplify drug delivery for patients with chronic conditions like diabetes, reducing reliance on needles and enhancing patient comfort.

Squid-Inspired Mechanism

The capsule mimics the propulsion system of cephalopods like squids and octopuses, which expel water through a siphon to generate movement or release ink to evade predators. Similarly, the capsule uses either compressed carbon dioxide or tightly coiled springs to eject liquid drugs at high velocity. A dissolvable carbohydrate trigger releases the stored energy upon exposure to the stomach’s humidity or acidity, ensuring precise drug delivery into the digestive tissue.

This jet-propulsion technique eliminates the need for microneedles, which were commonly used in previous oral drug delivery capsules. According to Graham Arrick, one of the lead authors, “Jets offer robustness in localization compared to needles, which require direct contact with tissues. This method allows most of the drug dose to be effectively delivered even from a slight distance or angle.”

Targeted Delivery and Design

The researchers developed two versions of the capsule for different parts of the digestive system. One, shaped like a blueberry with a flat bottom, delivers drugs downward into the stomach lining. The other, tube-shaped, aligns itself within tubular organs like the esophagus or intestine to eject drugs sideways. These capsules, made of metal and plastic, are excreted naturally after releasing their drug payload.

The blueberry-sized capsule can carry up to 80 microliters of drugs, while the tube-shaped version holds up to 200 microliters.

Promising Results in Animal Studies

In animal trials, the capsules successfully delivered insulin, GLP-1 receptor agonists (used to manage diabetes and obesity), and short interfering RNA (siRNA) — a potential treatment for genetic disorders. Drug concentrations in the bloodstream were comparable to those achieved via traditional injections, with no signs of tissue damage.

This technology offers a promising alternative for patients who frequently require injectable drugs, such as those managing diabetes. Not only does it eliminate the need for needles, but it also reduces the waste associated with disposable syringes.

Future Potential

In addition to home use, researchers envision an endoscope-compatible version for clinical settings, enabling precise drug delivery during medical procedures. Omid Veiseh, a bioengineering professor at Rice University not involved in the study, called the technology “a significant leap forward in oral drug delivery of macromolecule drugs,” noting its potential impact on biologics traditionally delivered via injections.

The research team is now working on refining the capsules for human trials. Funded by Novo Nordisk, MIT, Brigham and Women’s Hospital, and other organizations, this innovation promises to make needle-free drug delivery a reality, improving the quality of life for millions of patients worldwide.