Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Therapy in Mice and Swine
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
Grantová podpora
5-CDA-2020-947-A-N
JDRF - United States
1-19-ACE-31
American Diabetes Association Pathway Accelerator Award
1944875
National Science Foundation CAREER Award
National Institute for Research of Metabolic
LX22NPO5104
National Institute for Research of Metabolic and Cardiovascular Diseases of the Czech Republic (EXCELES)
RVO:6138963
Czech Academy of Sciences
2102-04994&2019PG-T1D016
Leona M. and Harry B. Helmsley Charitable Trust
PubMed
37994248
DOI
10.1002/adma.202308965
Knihovny.cz E-zdroje
- Klíčová slova
- bioconjugation, drug delivery, materials chemistry, nanotechnology,
- MeSH
- dendrimery * MeSH
- diabetes mellitus * MeSH
- glukosa MeSH
- inzulin MeSH
- krevní glukóza MeSH
- myši MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dendrimery * MeSH
- glukosa MeSH
- inzulin MeSH
- krevní glukóza MeSH
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.
CorVus Biomedical LLC Crawfordsville IN 47933 USA
Department of Chemical and Biomolecular Engineering 105 McCourtney Hall Notre Dame IN 46556 USA
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