Preventive Effects of Thermosensitive Biopolymer-Conjugated C-Peptide against High Glucose-Induced Endothelial Cell Dysfunction.
Macromol Biosci
; 19(9): e1900129, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31310433
ABSTRACT
C-peptide has emerged as a potential drug for treating diabetic complications. However, clinical application of C-peptide is limited by its short half-life during circulation and costly synthesis methods. To overcome these limitations, a biocompatible and thermosensitive biopolymer-C-peptide conjugate composed of human C-peptide genetically conjugated at the C-terminus of nine repeats of lysine-containing elastin-like polypeptide (K9-C-peptide) is generated. K9-C-peptide exhibits reversible thermal phase behavior with a transition temperature dependent on polypeptide concentration. Degradation of K9-C-peptide hydrogel depends on the concentration of four cleavage enzymes as well as the reaction time and frequency of treatments with elastase-2. The preventive effect of K9-C-peptide against high glucose-induced human aortic endothelial cell dysfunction is further investigated. K9-C-peptide inhibits high glucose-induced intracellular reactive oxygen species generation, transglutaminase 2 activation, and apoptosis, similar to the inhibitory effects of human C-peptide. Thus, K9-C-peptide is a potential drug depot for the sustained delivery of C-peptide to treat diabetic complications.
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Base de dados:
MEDLINE
Assunto principal:
Temperatura
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Biopolímeros
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Peptídeo C
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Células Endoteliais
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Glucose
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article