Control of blood glucose by novel GLP-1 delivery using biodegradable triblock copolymer of PLGA-PEG-PLGA in type 2 diabetic rats.
OBJECTIVE
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.
Choi
Suna
S
Center for Controlled Chemical Delivery (CCCD), Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Baudys
Miroslav
M
Kim
Sung Wan
SW
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003692:Delayed-Action Preparations; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005079:Excipients; D005934:Glucagon / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D020100:Hydrogels; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D019344:Lactic Acid; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D012995:Solubility
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D005079:Excipients; D020100:Hydrogels; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D011108:Polymers; D011498:Protein Precursors; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D052216:Glucagon-Like Peptide 1; D005934:Glucagon