Issue 97, 2016

Glucagon-like peptide-1 loaded phospholipid micelles for the treatment of type 2 diabetes: improved pharmacokinetic behaviours and prolonged glucose-lowering effects

Abstract

Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists are actively pursued as therapeutic agents for type 2 diabetes mellitus (T2DM). However, the therapeutic utility of GLP-1 is limited due to its rapid inactivation by dipeptidyl peptidase IV, and many GLP-1 receptor agonists suffer from innegligible adverse effects. In the present study, in order to develop long-acting GLP-1 derivatives with improved hypoglycemic activity, native GLP-1 (7-36)-NH2 was loaded into sterically stabilized phospholipid micelles (SSM), affording GLP-1-SSM. In vitro stability test and in vivo pharmacokinetic study demonstrated that the association of GLP-1 with SSM led to enhanced stability and drug utilization without affecting its insulinotropic and glucose-lowering activities. Single and multiple glucose tolerance tests confirmed that GLP-1-SSM was a long-acting antidiabetic agent comparable or even better than exendin-4. More importantly, preclinical studies found out that a chronic twice daily treatment of GLP-1-SSM in type 2 diabetic db/db mice suppressed body weight gain and food uptake, decreased HbA1c value, and restored the glucose tolerance ability. Collectively, our results suggest that GLP-1-SSM is a promising therapy for the treatment of T2DM and deserves further investigation.

Graphical abstract: Glucagon-like peptide-1 loaded phospholipid micelles for the treatment of type 2 diabetes: improved pharmacokinetic behaviours and prolonged glucose-lowering effects

Article information

Article type
Paper
Submitted
10 Sep 2016
Accepted
28 Sep 2016
First published
29 Sep 2016

RSC Adv., 2016,6, 94408-94416

Glucagon-like peptide-1 loaded phospholipid micelles for the treatment of type 2 diabetes: improved pharmacokinetic behaviours and prolonged glucose-lowering effects

X. Cui, Q. Meng, Y. Chu, X. Gu, Y. Tang, F. Zhou, Y. Fei, J. Fu and J. Han, RSC Adv., 2016, 6, 94408 DOI: 10.1039/C6RA22648E

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