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

TitleA depot-forming glucagon-like peptide-1 fusion protein reduces blood glucose for five days with a single injection
Publication TypeJournal Article
Year of Publication2013
AuthorsAmiram, M, Luginbuhl, KM, Li, X, Feinglos, MN, Chilkoti, A
JournalJournal of Controlled Release
Volume172
Issue1
Pagination144–151
Date Published8/2013
ISSN01683659
Abstract

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.

DOI10.1016/j.jconrel.2013.07.021
Short TitleJournal of Controlled Release