Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors
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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2022
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| Online Access: | https://hdl.handle.net/1721.1/141391 |
| _version_ | 1826198617196593152 |
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| author | Abramson, Alex Frederiksen, Morten Revsgaard Vegge, Andreas Jensen, Brian Poulsen, Mette Mouridsen, Brian Jespersen, Mikkel Oliver Kirk, Rikke Kaae Windum, Jesper Hubálek, František Water, Jorrit J Fels, Johannes Gunnarsson, Stefán B Bohr, Adam Straarup, Ellen Marie Ley, Mikkel Wennemoes Hvitfeld Lu, Xiaoya Wainer, Jacob Collins, Joy Tamang, Siddartha Ishida, Keiko Hayward, Alison Herskind, Peter Buckley, Stephen T Roxhed, Niclas Langer, Robert Rahbek, Ulrik Traverso, Giovanni |
| author_facet | Abramson, Alex Frederiksen, Morten Revsgaard Vegge, Andreas Jensen, Brian Poulsen, Mette Mouridsen, Brian Jespersen, Mikkel Oliver Kirk, Rikke Kaae Windum, Jesper Hubálek, František Water, Jorrit J Fels, Johannes Gunnarsson, Stefán B Bohr, Adam Straarup, Ellen Marie Ley, Mikkel Wennemoes Hvitfeld Lu, Xiaoya Wainer, Jacob Collins, Joy Tamang, Siddartha Ishida, Keiko Hayward, Alison Herskind, Peter Buckley, Stephen T Roxhed, Niclas Langer, Robert Rahbek, Ulrik Traverso, Giovanni |
| author_sort | Abramson, Alex |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:07:36Z |
| format | Article |
| id | mit-1721.1/141391 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:07:36Z |
| publishDate | 2022 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1413912022-03-30T03:26:35Z Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors Abramson, Alex Frederiksen, Morten Revsgaard Vegge, Andreas Jensen, Brian Poulsen, Mette Mouridsen, Brian Jespersen, Mikkel Oliver Kirk, Rikke Kaae Windum, Jesper Hubálek, František Water, Jorrit J Fels, Johannes Gunnarsson, Stefán B Bohr, Adam Straarup, Ellen Marie Ley, Mikkel Wennemoes Hvitfeld Lu, Xiaoya Wainer, Jacob Collins, Joy Tamang, Siddartha Ishida, Keiko Hayward, Alison Herskind, Peter Buckley, Stephen T Roxhed, Niclas Langer, Robert Rahbek, Ulrik Traverso, Giovanni 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. 2022-03-29T18:45:57Z 2022-03-29T18:45:57Z 2021 2022-03-29T18:37:59Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141391 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). en 10.1038/S41587-021-01024-0 Nature Biotechnology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC Prof. Traverso via Elizabeth Kuhlman |
| spellingShingle | Abramson, Alex Frederiksen, Morten Revsgaard Vegge, Andreas Jensen, Brian Poulsen, Mette Mouridsen, Brian Jespersen, Mikkel Oliver Kirk, Rikke Kaae Windum, Jesper Hubálek, František Water, Jorrit J Fels, Johannes Gunnarsson, Stefán B Bohr, Adam Straarup, Ellen Marie Ley, Mikkel Wennemoes Hvitfeld Lu, Xiaoya Wainer, Jacob Collins, Joy Tamang, Siddartha Ishida, Keiko Hayward, Alison Herskind, Peter Buckley, Stephen T Roxhed, Niclas Langer, Robert Rahbek, Ulrik Traverso, Giovanni Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title | Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title_full | Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title_fullStr | Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title_full_unstemmed | Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title_short | Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors |
| title_sort | oral delivery of systemic monoclonal antibodies peptides and small molecules using gastric auto injectors |
| url | https://hdl.handle.net/1721.1/141391 |
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