Kim Pyung-Hwan, Kim Sung Wan
Center for Controlled Chemical Delivery, Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
ISRN Endocrinol. 2012;2012:340632. doi: 10.5402/2012/340632. Epub 2012 May 30.
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.
肠促胰岛素激素，胰高血糖素样肽-1（GLP-1）及其受体激动剂（艾塞那肽-4），以其在葡萄糖稳态、促胰岛素分泌作用以及对体重减轻和食物摄入的影响而闻名。然而，由于二肽基肽酶-IV（DPP-IV）酶可使GLP-1迅速降解，且艾塞那肽-4经肾脏排泄，它们的临床应用受到了限制。尽管艾塞那肽-4的半衰期比GLP-1长，但仍需要频繁注射以维持治疗糖尿病的疗效。近几十年来，已开发出各种聚合物递送系统来递送GLP-1和艾塞那肽-4基因或肽，以实现其长期作用和在异位组织中的额外产生。在此，我们讨论了表达盒和肽的修饰，以实现天然肽的长期产生和分泌。此外，还描述了用于递送修饰后的GLP-1或艾塞那肽-4的非病毒或病毒系统的特性。此外，还讨论了与天然肽相比，近期通过与各种智能聚合物进行化学偶联来提高GLP-1或艾塞那肽-4肽生物半衰期的努力。
