Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Therapy in Mice and Swine.

Autor: Xian S; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Xiang Y; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Liu D; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Fan B; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Mitrová K; Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry, Prague, 16610, Czech Republic., Ollier RC; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Su B; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA., Alloosh MA; CorVus Biomedical, LLC, Crawfordsville, IN, 47933, USA., Jiráček J; Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry, Prague, 16610, Czech Republic., Sturek M; CorVus Biomedical, LLC, Crawfordsville, IN, 47933, USA., Alloosh M; CorVus Biomedical, LLC, Crawfordsville, IN, 47933, USA., Webber MJ; Department of Chemical & Biomolecular Engineering, 105 McCourtney Hall, Notre Dame, IN, 46556, USA.
Jazyk: angličtina
Zdroj: Advanced materials (Deerfield Beach, Fla.) [Adv Mater] 2024 Feb; Vol. 36 (5), pp. e2308965. Date of Electronic Publication: 2023 Dec 03.
DOI: 10.1002/adma.202308965
Abstrakt: The management of diabetes in a manner offering autonomous insulin therapy responsive to glucose-directed need, and moreover with a dosing schedule amenable to facile administration, remains an ongoing goal to improve the standard of care. While basal insulins with reduced dosing frequency, even once-weekly administration, are on the horizon, there is still no approved therapy that offers glucose-responsive insulin function. Herein, a nanoscale complex combining both electrostatic- and dynamic-covalent interactions between a synthetic dendrimer carrier and an insulin analogue modified with a high-affinity glucose-binding motif yields an injectable insulin depot affording both glucose-directed and long-lasting insulin availability. Following a single injection, it is even possible to control blood glucose for at least one week in diabetic swine subjected to daily oral glucose challenges. Measurements of serum insulin concentration in response to challenge show increases in insulin corresponding to elevated blood glucose levels, an uncommon finding even in preclinical work on glucose-responsive insulin. Accordingly, the subcutaneous nanocomplex that results from combining electrostatic- and dynamic-covalent interactions between a modified insulin and a synthetic dendrimer carrier affords a glucose-responsive insulin depot for week-long control following a single routine injection.
(© 2023 Wiley-VCH GmbH.)
Databáze: MEDLINE
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