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Improving Pharmacokinetics Reducing In Blood Glucose By Glucagon-Like Peptide-1 Using Albumin-Binding Domain.

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OBJECTIVE Frequent administrations for DPPIV-resistant GLP-1 analogs are necessary to maintain the blood concentrations due to short half-life of less than 5 minutes. However, most delivery systems that harbor ability… Click to show full abstract

OBJECTIVE Frequent administrations for DPPIV-resistant GLP-1 analogs are necessary to maintain the blood concentrations due to short half-life of less than 5 minutes. However, most delivery systems that harbor ability of sustainable release GLP-1 subject to low yield, high cost and undesirable side effects. Therefore, we aimed to prepare a simple and efficient delivery system that could be feasibly applied to reduce the blood glucose. METHODS A novel GLP-1 delivery system (GLP-1-ELPs-SA) was prepared and characterized by circular dichroism. Furthermore, the activity and property for GLP-1-ELPs-SA was evaluated in vitro and vivo. RESULTS GLP-1-ELPs-SA are easily expressed in E. coli in a soluble formulation and purified through inverse transition cycle. GLP-1-ELPs-SA could perform a subcutaneous depot under physiological conditions and was capable of slow release. GLP-1-ELPs-SA could also disperse into the blood vessels and showed high affinity to bind with mice (C57BL/6J) albumin, which endowed GLP-1-ELPs-SA with a long circulation in vivo. CONCLUSIONS Our delivery system could markedly decrease the clearance of recombinant proteins based on serum albumin, without substantially increasing the protein molecular weight and remarkably reducing the blood glucose within 120 h.

Keywords: delivery; reducing blood; blood; blood glucose; glp elps

Journal Title: Current pharmaceutical biotechnology
Year Published: 2019

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