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A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection.

Publication ,  Journal Article
Amiram, M; Luginbuhl, KM; Li, X; Feinglos, MN; Chilkoti, A
Published in: Journal of controlled release : official journal of the Controlled Release Society
November 2013

Peptide drugs are an exciting class of pharmaceuticals for the treatment of a variety of diseases; however, their short half-life dictates multiple and frequent injections causing undesirable side effects. Herein, we describe a novel peptide delivery system that seeks to combine the attractive features of prolonged circulation time with a prolonged release formulation. This system consists of glucagon-like peptide-1, a type-2 diabetes drug fused to a thermally responsive, elastin-like-polypeptide (ELP) that undergoes a soluble-insoluble phase transition between room temperature and body temperature, thereby forming an injectable depot. We synthesized a set of GLP-1-ELP fusions and verified their proteolytic stability and potency in vitro. Significantly, a single injection of depot forming GLP-1-ELP fusions reduced blood glucose levels in mice for up to 5 days, 120 times longer than an injection of the native peptide. These findings demonstrate the unique advantages of using ELPs to release peptide-ELP fusions from a depot combined with enhanced systemic circulation to create a tunable peptide delivery system.

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Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

November 2013

Volume

172

Issue

1

Start / End Page

144 / 151

Related Subject Headings

  • Recombinant Fusion Proteins
  • Phase Transition
  • Pharmacology & Pharmacy
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Injections
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1
 

Citation

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Amiram, M., Luginbuhl, K. M., Li, X., Feinglos, M. N., & Chilkoti, A. (2013). A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection. Journal of Controlled Release : Official Journal of the Controlled Release Society, 172(1), 144–151. https://doi.org/10.1016/j.jconrel.2013.07.021
Amiram, M., K. M. Luginbuhl, X. Li, M. N. Feinglos, and A. Chilkoti. “A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection.Journal of Controlled Release : Official Journal of the Controlled Release Society 172, no. 1 (November 2013): 144–51. https://doi.org/10.1016/j.jconrel.2013.07.021.
Amiram M, Luginbuhl KM, Li X, Feinglos MN, Chilkoti A. A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection. Journal of controlled release : official journal of the Controlled Release Society. 2013 Nov;172(1):144–51.
Amiram, M., et al. “A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection.Journal of Controlled Release : Official Journal of the Controlled Release Society, vol. 172, no. 1, Nov. 2013, pp. 144–51. Epmc, doi:10.1016/j.jconrel.2013.07.021.
Amiram M, Luginbuhl KM, Li X, Feinglos MN, Chilkoti A. A depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection. Journal of controlled release : official journal of the Controlled Release Society. 2013 Nov;172(1):144–151.
Journal cover image

Published In

Journal of controlled release : official journal of the Controlled Release Society

DOI

EISSN

1873-4995

ISSN

0168-3659

Publication Date

November 2013

Volume

172

Issue

1

Start / End Page

144 / 151

Related Subject Headings

  • Recombinant Fusion Proteins
  • Phase Transition
  • Pharmacology & Pharmacy
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Injections
  • Hypoglycemic Agents
  • Glucagon-Like Peptide 1