Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
received:
08
04
2020
accepted:
16
07
2021
pubmed:
1
9
2021
medline:
22
4
2022
entrez:
31
8
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34462588
doi: 10.1038/s41587-021-01024-0
pii: 10.1038/s41587-021-01024-0
pmc: PMC8766875
mid: NIHMS1732086
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents, Immunological
0
Capsules
0
Peptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
103-109Subventions
Organisme : NIBIB NIH HHS
ID : R01 EB000244
Pays : United States
Organisme : NIBIB NIH HHS
ID : R37 EB000244
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.
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