Polymer-based delivery of glucagon-like Peptide-1 for the treatment of diabetes.
The incretin hormones, glucagon-like peptide-1 (GLP-1) and its receptor agonist (exendin-4), are well known for glucose homeostasis, insulinotropic effect, and effects on weight loss and food intake. However, due to the rapid degradation of GLP-1 by dipeptidylpeptidase-IV (DPP-IV) enzyme and renal elimination of exendin-4, their clinical applications have been restricted. Although exendin-4 has longer half-life than GLP-1, it still requires frequent injections to maintain efficacy for the treatment of diabetes. In recent decades, various polymeric delivery systems have been developed for the delivery of GLP-1 and exendin-4 genes or peptides for their long-term action and the extra production in ectopic tissues. Herein, we discuss the modification of the expression cassettes and peptides for long-term production and secretion of the native peptides. In addition, the characteristics of nonviral or viral system used for a delivery of a modified GLP-1 or exendin-4 are described. Furthermore, recent efforts to improve the biological half-life of GLP-1 or exendin-4 peptide via chemical conjugation with various smart polymers via chemical conjugation compared with native peptide are discussed.
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Pyung-Hwan
PH
Kim
Sung Wan
SW
Kim