Application of elastin-like biopolymer-conjugated C-peptide hydrogel for systemic long-term delivery against diabetic aortic dysfunction. (December 2020)

• Record Type: Journal Article
• Authors: Lee, Ah-Jun; Lee, Yeon-Ju; Jeon, Hye-Yoon; Kim, Minsoo; Han, Eun-Taek; Park, Won Sun; Hong, Seok-Ho; Kim, Young-Myeong; Ha, Kwon-Soo
• Is Part Of: Acta biomaterialia. Volume 118(2020)
• Page Start: 32
• Page End: 43
• Publication Date: 2020-12
• Subjects: Elastin-like biopolymer -- Long-term delivery -- K9-C-peptide hydrogel -- Diabetes mellitus -- Vascular dysfunction; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1016/j.actbio.2020.09.055
• Languages: English
• ISSNs: 1742-7061

Abstract

Abstract: Due to their short half-lives, repeated administration of anti-hyperglycemic drugs can cause pain, discomfort, tissue damage, and infection in diabetic patients. Therefore, there is a need to develop long-term drug delivery systems to treat diabetes and its complications. C-peptide can prevent diabetic complications, including diabetic vasculopathy, but its clinical application is limited by its short half-life. Here, we developed K9-C-peptide (human C-peptide conjugated to an elastin-like biopolymer) and investigated its long-term influence on hyperglycemia-induced vascular dysfunction using an aortic endothelium model in diabetic mice. Using pharmacokinetics and in vivo imaging, we found that subcutaneously injected K9-C-peptide formed a hydrogel depot that slowly released human C-peptide into the blood circulation for 19 days. Administration of K9-C-peptide, human C-peptide, or K8 polypeptide had no effect on body weight or blood glucose levels. The slow release of C-peptide from K9-C-peptide hydrogels provided prolonged prevention of oxidative stress, inflammatory responses, and endothelial apoptosis in a hyperglycemia-induced vascular dysfunction model using the diabetic mouse aorta. Subcutaneous administration of unbound human C-peptide and K8 polypeptide were used as negative controls and had no effects. These results suggest that K9-C-peptide is suitable for the long-term delivery of human C-peptide for treating vascular dysfunction in diabetic patients. Graphical abstract: Image, graphical abstract