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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Amiram, M; Luginbuhl, KM; Li, X; Feinglos, MN; Chilkoti, A

Published Date

  • November 2013

Published In

Volume / Issue

  • 172 / 1

Start / End Page

  • 144 - 151

PubMed ID

  • 23928357

Pubmed Central ID

  • 23928357

Electronic International Standard Serial Number (EISSN)

  • 1873-4995

International Standard Serial Number (ISSN)

  • 0168-3659

Digital Object Identifier (DOI)

  • 10.1016/j.jconrel.2013.07.021

Language

  • eng