Evaluation of Strategies for Decreasing Blood Glucose Using Albuminbinding Domain

Objective: Frequent administrations for DPPIV-resistant GLP-1 analogs are necessary to maintain the blood concentrations due to the short half-life of less than 5 minutes. However, most delivery systems that possess the ability of sustainable release of GLP-1 have drawbacks such as 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 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 of GLP-1-ELPs-SA were evaluated in vitro and in vivo. Results: GLP-1-ELPs-SA are easily expressed in E. coli in a soluble formulation and purified through the inverse transition cycle. GLP-1-ELPs-SA spontaneously generated depot under physiological conditions. GLP-1-ELPs-SA was also found to be dispersed in the blood vessels from the depot and showed a high affinity to bind with mice (C57BL/6J) albumin, which shows that GLP-1-ELPs-SA has a long circulation time in vivo. Conclusion: 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.