Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 107, Issue 5, Pages 1107-1113Publisher
WILEY
DOI: 10.1002/jbm.a.36647
Keywords
injectable hydrogel; polyion complex flower micelle; type 2 diabetes; reactive oxygen species; exenatide
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan [25220203]
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To provide sustained release of exenatide and enhance therapeutic efficacy for the treatment of type 2 diabetes compared to the existing products for exenatide, we developed an exenatide-loaded, redox-active, injectable gel (Exe@RIG). This injectable gel is formed by a polyion complex (PIC) comprising three components, (1) cationic polyamine-poly(ethylene glycol)-polyamine triblock copolymer possessing reactive oxygen species (ROS)-scavenging moieties as side chains, (2) anionic poly(acrylic acid), and (3) exenatide. The mixture formed exenatide-loaded PIC flower micelles at room temperature, which immediately converted to a gel under physiological conditions. Owing to electrostatic interactions between exenatide and the PIC gel network, RIG was able to provide sustained release of exenatide without a significant initial burst. Subcutaneous injection of Exe@RIG once a week prevented the increase in glucose concentration significantly in db/db mice compared to those in control groups. In addition, Exe@RIG suppressed the degeneration of pancreatic islets, which is reported to be caused by increased ROS. Our result indicates that Exe@RIG has the potential to provide a long acting exenatide as well as enhanced efficacy in the treatment of type 2 diabetes compared to the existing products. (c) 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1107-1113, 2019.
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