Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery

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Date

2018-05-01

Author

Lee, Juneyoung
Ko, Jeong Hoon
Mansfield, Kathryn M.
Nauka, Peter C.
Bat, Erhan
Maynard, Heather D.

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Effective delivery of therapeutic proteins is important for many biomedical applications. Yet, the stabilization of proteins during delivery and long-term storage remains a significant challenge. Herein, a trehalose-based hydrogel is reported that stabilizes insulin to elevated temperatures prior to glucose-triggered release. The hydrogel is synthesized using a polymer with trehalose side chains and a phenylboronic acid end-functionalized 8-arm poly(ethylene glycol) (PEG). The hydroxyls of the trehalose side chains form boronate ester linkages with the PEG boronic acid cross-linker to yield hydrogels without any further modification of the original trehalose polymer. Dissolution of the hydrogel is triggered upon addition of glucose as a stronger binder to boronic acid (K-b = 2.57 vs 0.48 M-1 for trehalose), allowing the insulin that is entrapped during gelation to be released in a glucose-responsive manner. Moreover, the trehalose hydrogel stabilizes the insulin as determined by immunobinding after heating up to 90 degrees C. After 30 min heating, 74% of insulin is detected by enzyme-linked immunosorbent assay in the presence of the trehalose hydrogel, whereas only 2% is detected without any additives.

Subject Keywords

Biotechnology, Materials Chemistry, Bioengineering, Polymers and Plastics, Biomaterials

URI

https://hdl.handle.net/11511/37535

Journal

MACROMOLECULAR BIOSCIENCE

DOI

https://doi.org/10.1002/mabi.201700372

Collections

Department of Chemical Engineering, Article

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Citation Formats

J. Lee, J. H. Ko, K. M. Mansfield, P. C. Nauka, E. Bat, and H. D. Maynard, “Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery,” MACROMOLECULAR BIOSCIENCE, pp. 0–0, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/37535.