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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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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-(-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.

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Authors and Affiliations

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

    Suna Choi & Sung Wan Kim

  2. MacroMed, Inc, Sandy, sUtah, 84070, USA

    Miroslav Baudys

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  1. Suna Choi
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  2. Miroslav Baudys
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  3. Sung Wan Kim
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Correspondence to Sung Wan Kim.

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Choi, S., Baudys, M. & Kim, S.W. Control of Blood Glucose by Novel GLP-1 Delivery Using Biodegradable Triblock Copolymer of PLGA-PEG-PLGA in Type 2 Diabetic Rats. Pharm Res 21, 827–831 (2004). https://doi.org/10.1023/B:PHAM.0000026435.27086.94

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  • DOI: https://doi.org/10.1023/B:PHAM.0000026435.27086.94

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