Glucose-Responsive Trehalose Hydrogel for Insulin Stabilization and Delivery


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Lee J., Ko J. H., Mansfield K. M., Nauka P. C., Bat E., Maynard H. D.

MACROMOLECULAR BIOSCIENCE, vol.18, no.5, 2018 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 18 Issue: 5
  • Publication Date: 2018
  • Doi Number: 10.1002/mabi.201700372
  • Journal Name: MACROMOLECULAR BIOSCIENCE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: biomaterials, drug delivery systems, hydrogels, proteins, stabilization, BORONIC ACID, PROTEIN STABILIZATION, THERAPEUTIC PROTEIN, PUMP THERAPY, COMPLEXATION, PH, GLYCOPOLYMERS, GLYCOPROTEINS, RECEPTORS, STABILITY
  • Middle East Technical University Affiliated: Yes

Abstract

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.