A new type of drug delivery device in development could someday bypass the challenges and fears associated with certain types of injectable drugs. In collaboration with Novo Nordisk, researchers at the Massachusetts Institute of Technology (MIT) have designed a groundbreaking needle-free microjet drug delivery system. Inspired by the jet propulsion mechanisms of squid, this technology, inside a capsule that the patient swallows, delivers drugs directly into the gastrointestinal (GI) tract, offering a safer and more efficient alternative to subcutaneous pen injections.
“Needles require specialized training to administer, present challenges with safe disposal, and carry the risk of needle-stick injuries, whether used externally or for deeper, internal applications,” explained MIT engineer Giovanni Traverso, one of the project’s lead scientists.
The ingestible capsule dissolves when it reaches the target pH inside the GI tract. Then, the microjet device uses high-pressure bursts to deliver macromolecule therapies, such as insulin and glucagon-like peptide-1 (GLP-1) analogs, deep into target tissues. Unlike other ingestible devices that rely on needles, this innovation bypasses the risks associated with sharp instruments while potentially improving patient compliance.
A Novel, Creative Design
“This is the first study demonstrating the use of microjets for delivery of drugs into the gastrointestinal tract,” remarked Samir Mitragotri, a Harvard researcher who was not involved in the project. “All in all, this is a very creative design.”
The microjet devices, known as MiDe systems, are tailored for specific GI regions. Researchers developed four device configurations: two autonomous models and two designed for endoscopic guidance. The devices deliver jets in both radial and axial directions, targeting tubular areas like the small intestine and broader regions like the stomach, respectively.
The key to their success is a precise balance between jet pressure and safety. Too much force could damage tissues, while too little would limit drug absorption. To address this, the researchers calibrated the devices through extensive in vitro and ex vivo testing. They then conducted in vivo tests in research animals, and the results showed high bioavailability of the drugs delivered by the microjets.
Remarkable Results
Tests revealed that MiDe systems achieved drug absorption rates comparable to subcutaneous injections. For instance, an endoscopic radial MiDe device targeting the intestines delivered a GLP-1 analog with 67% bioavailability in animal models. Another MiDe device achieved even more impressive results. The endoscopic axial MiDe device achieved 82% bioavailability for a small interfering RNA (siRNA) compound in the same organ.
Autonomous MiDe devices also showed promise, with bioavailability rates of 31% and 23% for insulin delivered by the autonomous radial and axial devices, respectively. The stability and precision of these systems was confirmed through high-speed imaging and histological analysis, which demonstrated that the jets penetrated deep into target tissues without causing damage.
Expanding Possibilities and Next Steps
The potential of these microjets extends beyond insulin and RNA delivery. The system could pave the way for administering monoclonal antibodies and other biologic therapies currently restricted to injections. The research team also highlighted the possibility of tailoring the technology to accommodate larger molecules and broad therapeutic windows.
Future development will focus on miniaturizing the devices to reduce the risk of obstruction in the GI tract, optimizing activation mechanisms, and ensuring compatibility with biodegradable materials. The researchers noted that only one of the models is within the size of ingestible devices previously approved by the US Food and Drug Administration for regular dosing. They suggest that reducing or dividing a dose into multiple smaller devices would help achieve this. Addressing patient-specific factors such as anatomy and co-morbidities will also be crucial for widespread adoption.
While the technology is still experimental and far from human trials, its implications are profound. By achieving high systemic bioavailability through the oral route, the MiDe platform could offer a viable alternative to traditional injections. With further optimization and rigorous testing, these squid-inspired microjets could redefine how some medicines are delivered, providing a needle-free solution for a wide range of treatments.
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