Use of a biomimetic hydrogel depot technology for sustained delivery of GLP-1 receptor agonists reduces burden of diabetes management.

Autor:	d'Aquino AI; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA., Maikawa CL; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA., Nguyen LT; Department of Biochemistry, Stanford University, Palo Alto, CA 94305, USA., Lu K; Department of Biology, Stanford University, Stanford, CA 94305, USA., Hall IA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA., Jons CK; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA., Kasse CM; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA., Yan J; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA., Prossnitz AN; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA., Chang E; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA., Baker SW; Department of Comparative Medicine, Stanford University, Palo Alto, CA 94305, USA., Hovgaard L; Department of Biophysics and Formulations, Global Research Technologies, Novo Nordisk Park, 2760 Maaloev, Denmark., Steensgaard DB; Department of Biophysics and Formulations, Global Research Technologies, Novo Nordisk Park, 2760 Maaloev, Denmark., Andersen HB; Department of Biophysics and Formulations, Global Research Technologies, Novo Nordisk Park, 2760 Maaloev, Denmark., Simonsen L; Department of Obesity Research, Global Drug Discovery, Novo Nordisk Park, 2760 Maaloev, Denmark., Appel EA; Department of Materials Science & Engineering, Stanford University, Stanford, CA 94025, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; ChEM-H Institute, Stanford University, Stanford, CA 94305, USA; Department of Pediatrics (Endocrinology), Stanford University, Stanford, CA 94305, USA; Woods Institute for the Environment, Stanford University, Stanford, CA 94305, USA. Electronic address: eappel@stanford.edu.
Jazyk:	angličtina
Zdroj:	Cell reports. Medicine [Cell Rep Med] 2023 Nov 21; Vol. 4 (11), pp. 101292.
DOI:	10.1016/j.xcrm.2023.101292
Abstrakt:	Glucagon-like peptide-1 (GLP-1) is an incretin hormone and neurotransmitter secreted from intestinal L cells in response to nutrients to stimulate insulin and block glucagon secretion in a glucose-dependent manner. Long-acting GLP-1 receptor agonists (GLP-1 RAs) have become central to treating type 2 diabetes (T2D); however, these therapies are burdensome, as they must be taken daily or weekly. Technological innovations that enable less frequent administrations would reduce patient burden and increase patient compliance. Herein, we leverage an injectable hydrogel depot technology to develop a GLP-1 RA drug product capable of months-long GLP-1 RA delivery. Using a rat model of T2D, we confirm that one injection of hydrogel-based therapy sustains exposure of GLP-1 RA over 42 days, corresponding to a once-every-4-months therapy in humans. Hydrogel therapy maintains management of blood glucose and weight comparable to daily injections of a leading GLP-1 RA drug. This long-acting GLP-1 RA treatment is a promising therapy for more effective T2D management. Competing Interests: Declaration of interests A.I.D., C.L.M., L.T.N., and E.A.A. are listed on a patent describing the technology reported in this work. L.H., D.B.S., and H.B.A. declare the following potential competing interest with respect to the research, authorship, and/or publication of this article: the authors are full-time employees and shareholders of Novo Nordisk A/S. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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