Cephalopod-inspired jetting devices for gastrointestinal drug delivery

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract<sup>1-3</sup>, through recent developments in ingestible robotic devices<sup>4-7</sup>. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract. Furthermore, they are implemented in both tethered and ingestible formats, facilitating endoscopic applications or patient self-dosing. Our study identified suitable pressure and nozzle dimensions for different segments of the gastrointestinal tract and applied microjets in a variety of devices that support delivery across the various anatomic segments of the gastrointestinal tract. We characterized the ability of these systems to administer macromolecules, including insulin, a glucagon-like peptide-1 (GLP1) analogue and a small interfering RNA (siRNA) in large animal models, achieving exposure levels similar to those achieved with subcutaneous delivery. This research provides key insights into jetting design parameters for gastrointestinal administration, substantially broadening the possibilities for future endoscopic and ingestible drug delivery devices.

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Publication Details

Journal
Nature
Published
2024-11-20
DOI
https://doi.org/10.1038/s41586-024-08202-5
Citations
43
Primary Topic
Pancreatic function and diabetes
Type
article
Field-Weighted Citation Impact
24.63
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article

Cephalopod-inspired jetting devices for gastrointestinal drug delivery

Aghiad Ghazal, Yi‐Chun Lu, David Schultz, N. E. Egecioglu et al.
43 citations
Nature
Pancreatic function and diabetes
24.63
article

Cephalopod-inspired jetting devices for gastrointestinal drug delivery

Aghiad Ghazal, Yi‐Chun Lu, David Schultz, N. E. Egecioglu, Charlotte M. Dalsgaard, Maria Pereverzina, Niclas Roxhed, Graham Arrick, Torben Sebastian Last, Ulrik L. Rahbek, Giovanni Battista Traverso, Mette H. Poulsen, Jorrit J. Water, Julian Jepsen, Siddharth Tamang, Seokkee Min, Johannes Kuosmanen, Morten Revsgaard Frederiksen, Stefán B. Gunnarsson, Drago Sticker, Jason Li, Cody Cleveland, Paramesh Karandikar, Rikke Kaae Kirk, Kaitlyn Hess, Brian Mouridsen, Joy Collins, Adam Bohr, Alison Hayward, Stephen T. Buckley, Jacob Wainer, D. Gwynne, Henrik D. Pedersen, Siming You, Peter F. Herskind, Keiko Ishida, A. Azzarello, Todd Duncombe, Anders H. Uhrenfeldt, C.J. Anker, Enrique M. D. Alba, I. Patsi
article en
43 citations

Abstract

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract<sup>1-3</sup>, through recent developments in ingestible robotic devices<sup>4-7</sup>. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract. Furthermore, they are implemented in both tethered and ingestible formats, facilitating endoscopic applications or patient self-dosing. Our study identified suitable pressure and nozzle dimensions for different segments of the gastrointestinal tract and applied microjets in a variety of devices that support delivery across the various anatomic segments of the gastrointestinal tract. We characterized the ability of these systems to administer macromolecules, including insulin, a glucagon-like peptide-1 (GLP1) analogue and a small interfering RNA (siRNA) in large animal models, achieving exposure levels similar to those achieved with subcutaneous delivery. This research provides key insights into jetting design parameters for gastrointestinal administration, substantially broadening the possibilities for future endoscopic and ingestible drug delivery devices.

NatureVol. 636(8042)
Broad Institute (US), Brigham and Women's Hospital (US), Harvard University (US), Novo Nordisk (Denmark) (DK), Novo Nordisk (Switzerland) (CH), Novo Nordisk (Germany) (DE), Massachusetts Institute of Technology (US), KTH Royal Institute of Technology (SE)
Good health and well-being
Openalex Percentile: Top 0%
Pancreatic function and diabetes
24.63
DOIOpen Access PDFOpenAlex
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