, Volume 21, Issue 5, pp 827-831

Control of Blood Glucose by Novel GLP-1 Delivery Using Biodegradable Triblock Copolymer of PLGA-PEG-PLGA in Type 2 Diabetic Rats

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Purpose. The incretin hormone glucagon-like peptide-1 (GLP-1) is a promising candidate for treatment of type 2 diabetes mellitus. However, plasma half-life of GLP-1 is extremely short, thus multiple injections or continuous infusion is required for therapeutic use of GLP-1. Therefore, we investigated a new delivery system as a feasible approach to achieve sustained GLP-1 release for a 2-week period.

Methods. A water-soluble, biodegradable triblock copolymer of poly [(dl-lactide-co-glycolide)-b-ethylene glycol-b-(-lactide-co-glycolide)] (ReGel) was used in this study as an injectable formulation for controlled release of GLP-1. GLP-1 was formulated into ReGel as insoluble zinc complex to stabilize GLP-1 against aggregation and slow down release. The GLP-1 release profile was monitored in vitro and in vivo. Zucker Diabetic Fatty rats were administered subcutaneously with the GLP-1 formulation. The concentration of GLP-1, insulin, and glucose was monitored every day after the GLP-1 administration.

Results. The GLP-1 release from ReGel formulation in vitro and in vivo showed no initial burst and constant release for 2 weeks. Animal study demonstrated that the plasma insulin level was increased, and the blood glucose level was controlled for 2 weeks by one injection of ReGel/ ZnGLP-1 formulation.

Conclusions. It is concluded that one injection of zinc-complexed GLP-1 loaded ReGel can be used for delivery of bioactive GLP-1 during a 2-week period. Because this new delivery system is biocompatible and requires twice-a-month injection, it can improve patient compliance and cost-effectiveness.