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Hyaluronic Acid Based Drug Delivery System for the Treatment of Type 2 Diabetes

Title
Hyaluronic Acid Based Drug Delivery System for the Treatment of Type 2 Diabetes
Authors
공지현
Date Issued
2010
Publisher
포항공과대학교
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 novel 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 bioconjugation 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 novel HA ? exendin 4 conjugates will be investigated further as a twice a week injection dosage form for clinical applications.
URI
http://postech.dcollection.net/jsp/common/DcLoOrgPer.jsp?sItemId=000000546338
http://oasis.postech.ac.kr/handle/2014.oak/567
Article Type
Thesis
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