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Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
Name
Liquid SOMA paper For Pub v1-1.pdf
Description
Accepted version
Size
2 MB
Format
Adobe PDF
Checksum (MD5)
8d1f16e16c8707061bbe6ad09530b3d2
Author(s)
Abramson, Alex
Frederiksen, Morten Revsgaard
Vegge, Andreas
Jensen, Brian
Poulsen, Mette
Mouridsen, Brian
Jespersen, Mikkel Oliver
Kirk, Rikke Kaae
Windum, Jesper
Hubálek, František
Date Issued
2021
Journal
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Citation
Abramson, Alex, Frederiksen, Morten Revsgaard, Vegge, Andreas, Jensen, Brian, Poulsen, Mette et al. 2021. "Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors." Nature Biotechnology, 40 (1).
Version
Author's final manuscript
Abstract
Oral administration provides a simple and non-invasive approach for drug delivery. However, due to poor absorption and swift enzymatic degradation in the gastrointestinal tract, a wide range of molecules must be parenterally injected to attain required doses and pharmacokinetics. Here we present an orally dosed liquid auto-injector capable of delivering up to 4-mg doses of a bioavailable drug with the rapid pharmacokinetics of an injection, reaching an absolute bioavailability of up to 80% and a maximum plasma drug concentration within 30 min after dosing. This approach improves dosing efficiencies and pharmacokinetics an order of magnitude over our previously designed injector capsules and up to two orders of magnitude over clinically available and preclinical chemical permeation enhancement technologies. We administered the capsules to swine for delivery of clinically relevant doses of four commonly injected medications, including adalimumab, a GLP-1 analog, recombinant human insulin and epinephrine. These multi-day dosing experiments and oral administration in awake animal models support the translational potential of the system.
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
10.1038/S41587-021-01024-0
