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Glucose Uptake Measurement and Response to Insulin Stimulation in In Vitro Cultured Human Primary Myotubes

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Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery.

Juneyoung Lee^1,2, Jeong Hoon Ko^1,2, Kathryn M Mansfield^1,2

¹Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, CA, 90095-1569, USA.

Macromolecular Bioscience

|April 18, 2018

Summary

This study introduces a novel trehalose-based hydrogel for stabilizing therapeutic proteins like insulin. The hydrogel protects insulin from heat and enables glucose-responsive release, addressing key challenges in protein delivery.

Keywords:

biomaterials drug delivery systems hydrogels proteins stabilization

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Area of Science:

Biomaterials Science
Drug Delivery Systems
Protein Stabilization

Background:

Effective delivery of therapeutic proteins is crucial for biomedical applications.
Stabilizing proteins during delivery and storage presents a significant challenge.
Current methods often struggle with maintaining protein integrity under various conditions.

Purpose of the Study:

To develop a novel hydrogel system for enhanced protein stabilization and controlled release.
To investigate the glucose-responsive release mechanism of entrapped proteins.
To evaluate the thermal stability of insulin within the developed hydrogel.

Main Methods:

Synthesis of a trehalose-based hydrogel using a polymer with trehalose side chains and phenylboronic acid-functionalized 8-arm poly(ethylene glycol) (PEG).
Formation of boronate ester linkages between trehalose hydroxyls and PEG boronic acid for hydrogel cross-linking.
Assessment of glucose-triggered hydrogel dissolution and insulin release kinetics.
Evaluation of insulin stability via immunobinding assays after thermal stress.

Main Results:

A trehalose-based hydrogel was successfully synthesized, stabilizing insulin effectively.
The hydrogel demonstrated glucose-responsive insulin release, with glucose acting as a stronger binder to boronic acid.
Insulin entrapped in the hydrogel showed significant thermal stabilization, with 74% detected after 30 min heating at 90 °C, compared to 2% without the hydrogel.

Conclusions:

The developed trehalose-hydrogel system offers a promising approach for stabilizing therapeutic proteins, such as insulin, against thermal degradation.
The glucose-triggered release mechanism provides a controllable method for protein delivery.
This innovation has significant implications for improving the efficacy and shelf-life of protein-based therapeutics.