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Pharm Res. 2004 May;21(5):827-31.

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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1
Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.

Abstract

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-(DL-lactide-coglycolide)] (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.

PMID:
15180341
[Indexed for MEDLINE]
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