Open AccessOral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
Author(s) -
Alex Abramson,
Morten Revsgaard Frederiksen,
Andreas Vegge,
Brian Jensen,
Mette H. Poulsen,
Brian Mouridsen,
Mikkel Oliver Jespersen,
Rikke Kaae Kirk,
Jesper Windum,
František Hubálek,
Jorrit J. Water,
Johannes Fels,
Stefán B Gunnarsson,
Adam Bohr,
Ellen Marie Straarup,
Mikkel Wennemoes Hvitfeld Ley,
Xianping Lu,
Jacob Wainer,
Joy Collins,
Siddartha Tamang,
Keiko Ishida,
Alison Hayward,
Peter F. Herskind,
Stephen T. Buckley,
Niclas Roxhed,
Robert Langer,
Ulrik Lytt Rahbek,
Giovanni Traverso
Publication year - 2021
Publication title -
nature biotechnology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.358
H-Index - 445
eISSN - 1546-1696
pISSN - 1087-0156
DOI - 10.1038/s41587-021-01024-0
Subject(s) - pharmacokinetics , bioavailability , dosing , pharmacology , oral administration , medicine , drug , drug delivery , gastrointestinal tract , chemistry , organic chemistry
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.