Hypodermic and endoscopic needles are widely used to deliver medications. However, needle-based therapeutics require training to safely handle and dispose of devices that could pierce the skin, and studies show that patients who frequently receive injections prefer alternatives like oral medications. Autonomous, needle-free systems that can penetrate tissue and administer drugs could help overcome these challenges.
To address this need, investigators at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, along with co-authors at MIT and Novo Nordisk, have developed a family of microjet delivery (MiDe) systems. Inspired by how squids can release controlled jets of ink, the scientists created MiDe devices that could discharge liquid drugs along different directions to precisely target distinct segments of the gastrointestinal (GI) tract. This enabled the tailored delivery of drugs within varied regions of the GI tract, such as the globular stomach or narrow intestine, without damaging their walls. Results are published in Nature.
“Our research provides key insights into GI microjet administration and substantially broadens the possibilities for future endoscopic and ingestible drug delivery devices,” said senior author Giovanni Traverso, MB, BChir, PhD of the Brigham’s Division of Gastroenterology, Hepatology and Endoscopy. “Future work could test additional therapeutic agents and explore translation to humans.”
The design includes devices of two different orientations: axial systems, which can orient within larger spaces like the stomach or colon, and radial systems, which can direct jets within narrower regions like the esophagus or small intestine. In addition, MiDe systems are designed to be swallowed for self-use or connected to tools used in endoscopy for controlled delivery.
After first characterizing the systems in the lab, the research team performed a series of experiments using swine tissue to determine parameters like the optimal nozzle dimensions and jetting pressure for different GI regions. Using these results, they implemented varied MiDe systems in large animal models to deliver macromolecules such as insulin and a glucagon-like peptide-1 analogue. The researchers observed that the tethered devices successfully released drug doses comparable to subcutaneous injections in humans.
As a proof-of-concept, the authors also demonstrated in a preclinical study that an orally ingested, pH-sensitive capsule could deliver a targeted payload in the small intestine before exiting the GI tract. The team plans to conduct further testing on additional therapeutic agents in animal models and in the lab.
Authorship: In addition to Traverso, BWH authors include K. Hess, K. Ishida, A. Hayward, and S. You.
Funding: This study was funded by Novo Nordisk A/S. Additionally, Traverso and his laboratory were supported in part by Karl van Tassel (1925), Career Development Professorship, the Department of Mechanical Engineering, Massachusetts Institute of Technology (MIT) and the Division of Gastroenterology, Brigham and Women’s Hospital, the Advanced Research Projects Agency for Health (ARPA-H) under Award Number D24AC00040-00. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Advanced Research Projects Agency for Health
Disclosures: D. Sticker, A. Ghazal, T. Duncombe, B. Mouridsen, J. P. H. Jepsen, D. Schultz, E. Medina De Alba, M. Poulsen, C. Anker, H. D. Pedersen, N. E. Egecioglu, C. Cleveland, A. H. Uhrenfeldt, M. Pereverzina, R. K. Kirk, C. M. Dalsgaard, S. B. Gunnarsson, I. Patsi, A. Bohr, A. Azzarello, M. R. Frederiksen, P. Herskind, U. L. Rahbek, J. J. Water, and S. T. Buckley are employees and shareholders of Novo Nordisk. J. Wainer is an employee and shareholder of Fractyl Health Inc. S.Min is affiliated with Brown University, and is no longer affiliated with MIT at the time of submission. P. Karandikar is affiliated with T.H. Chan School of Medicine, University of Massachusetts, USA. G. Traverso has received consulting fees and grant funding from Novo Nordisk. B. Mouridsen, J.P.H. Jepsen and M.R. Frederiksen are inventors of the following patent: Jensen, B. et al. Medical device with actuation mechanism. WO2020157324, 06 August 2020. G.AD. Sticker, A. Ghazal, Y. Lu, D. Gwynne, B. Mouridsen, J. Wainer, J. P. H. Jepsen, T. S. Last, C. Cleveland, S. You, A. Bohr, N. Roxhed, J. J. Water, and G. Traverso are inventors of the following patent: Arrick, G. et al. Drug delivery device. WO2022034041, 17 February 2022. G. Arrick, D. Sticker, A. Ghazal, D. Gwynne, J. Wainer, J. P. H. Jepsen, M. Poulsen, C. Cleveland, J. J. Water, and G. Traverso are inventors of the following patent: Traverso, G. et al. Ingestible drug delivery device. WO2022035750, 17 February 2022.
Paper cited: Arrick G et al. “Cephalopod-inspired jetting devices for gastrointestinal drug delivery” Nature DOI: 10.1038/s41586-024-08202-5
