Long Acting Hyaluronate-Exendin 4 Conjugate for the Treatment of Type 2 Diabetes
SCIE
SCOPUS
- Title
- Long Acting Hyaluronate-Exendin 4 Conjugate for the Treatment of Type 2 Diabetes
- Authors
- Kong, JH; Oh, EJ; Chae, SY; Lee, KC; Hahn, SK
- Date Issued
- 2010-05
- Publisher
- ELSEVIER SCIENCE BV
- Abstract
- Despite clinical exploitation of exendin 4 for the treatment of type 2 diabetes, the significantly short half-life requiring twice a day injection has limited the wide applications. In this work, a protocol for the synthesis of long acting hyaluronate (HA) - exendin 4 conjugate was successfully developed using Michael addition chemistry between vinyl sulfone modified HA (HA-VS) and thiolated exendin 4. The exendin 4 content could be controlled in the range of 5-30 molecules per single HA chain with a bio-conjugation efficiency higher than 90%. The conjugation of exendin 4 with HA resulted in about 20 times improved in vitro serum stability maintaining the hypoglycemic and gluco-regulatory bioactivities of exendin 4. HA - exendin 4 conjugates showed excellent glucose-lowering capabilities in type 2 db/db mice demonstrating protracted hypoglycemic effect up to 3 days after a single subcutaneous injection. Furthermore, insulin immunohistochemical analysis of islets in db/db mice confirmed the improved insulinotropic activity of HA - exendin 4 conjugates. The HA - exendin 4 conjugates will be investigated further as a twice a week injection dosage form for clinical applications. (C) 2010 Elsevier Ltd. All rights reserved.
- Keywords
- Hyaluronic acid; Exendin-4; Conjugation; Drug delivery; Type 2 diabetes; ACID HYDROGELS; EXENATIDE EXENDIN-4; QUANTUM DOTS; PEPTIDE; DEGRADATION; PEGYLATION; CHEMISTRY; RECEPTOR; ANALOGS; WEIGHT
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/25897
- DOI
- 10.1016/J.BIOMATERIALS.2010.01.091
- ISSN
- 0142-9612
- Article Type
- Article
- Citation
- BIOMATERIALS, vol. 31, no. 14, page. 4121 - 4128, 2010-05
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