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

0582819 - ÚOCHB 2025 RIV US eng J - Journal Article
Xian, S. - Xiang, Y. - Liu, D. - Fan, B. - Mitrová, Katarína - Ollier, R. C. - Su, B. - Alloosh, M. A. - Jiráček, Jiří - Sturek, M. - Alloosh, M. - Webber, M. J.
Insulin-Dendrimer Nanocomplex for Multi-Day Glucose-Responsive Therapy in Mice and Swine.
Advanced Materials. Roč. 36, č. 5 (2024), č. článku 2308965. ISSN 0935-9648. E-ISSN 1521-4095
R&D Projects: GA MŠMT(CZ) LX22NPO5104
Institutional support: RVO:61388963
Keywords : drug delivery * nanotechnology * materials chemistry * bioconjugation
Impact factor: 29.4, year: 2022
Method of publishing: Limited access
https://doi.org/10.1002/adma.202308965

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.
Permanent Link: https://hdl.handle.net/11104/0350871