Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions

Tamar Traitel, Yachin Cohen, Joseph Kost

Research output: Contribution to journalArticlepeer-review

212 Scopus citations

Abstract

We studied the glucose-responsive insulin controlled release system based on the hydrogel poly(2-hydroxyethyl methacrylate-co-N,N- dimethylaminoethyl methacrylate), also called poly(HEMA-co-DMAEMA), with entrapped glucose oxidase, catalase and insulin. When exposed to physiological fluids, glucose diffuses into the hydrogel, glucose oxidase catalyzes the glucose conversion to gluconic acid, causing swelling of the pH-sensitive hydrogel and subsequently increased insulin release. The higher the glucose concentration in the medium, the higher and faster the swelling and release rates. The effects of polymer morphology and oxygen availability on hydrogel swelling and on insulin release kinetics were tested. Polymer morphology was modified by changing the crosslinking agent (tetraethylene glycol dimethacrylate) concentration (0-0.95 vol%). Oxygen availability was modified by changing the immobilized catalase concentration (0-15 units catalase per unit glucose oxidase) and by bubbling oxygen through the medium. The results indicated that: (i) Hydrogels without crosslinking agent were found to be stable in water, and their sensitivity to pH and glucose was higher than the chemically crosslinked hydrogels. (ii) Immobilization of catalase in addition to glucose oxidase in hydrogels prepared without crosslinking agent, resulted in enhanced swelling kinetic. In addition, we carried out primary in vivo experiments on rats, which demonstrated that at least some of the entrapped insulin retains its active form and is effective in reducing blood glucose levels. Moreover, no tissue encapsulation was observed around matrices implanted in the peritoneum. In conclusion, the pH- sensitive hydrogel poly(HEMA-co-DMAEMA) can be manipulated to produce glucose-responsive insulin release system that is effective in reducing blood glucose levels. (C) 2000 Elsevier Science Ltd.

Original languageEnglish
Pages (from-to)1679-1687
Number of pages9
JournalBiomaterials
Volume21
Issue number16
DOIs
StatePublished - 1 Aug 2000

Keywords

  • Catalase
  • Glucose oxidase
  • Glucose- responsive polymers
  • Hydrogels
  • Insulin release
  • Swelling

Fingerprint

Dive into the research topics of 'Characterization of glucose-sensitive insulin release systems in simulated in vivo conditions'. Together they form a unique fingerprint.

Cite this