Abstract
The GLP1-receptor agonists exert regulatory key roles in diabetes, obesity and related complications. Here we aimed to develop polymeric microparticles loaded with homologous human GLP1 (7-37) or the analogue liraglutide. Peptide-loaded microparticles were prepared by a double emulsion and solvent evaporation process with a set of eight polymers based on lactide (PLA) or lactide-glycolide (PLGA), and evaluated for particle-size distribution, morphology, in vitro release and pharmacologic activity in mice. The resulting microparticles showed size distribution of about 30–50 μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30–40 days. In vivo evaluation in Swiss male mice revealed a similar extension of glycemic and body weight gain modulation for up to 25 days after a single subcutaneous administration of either hGLP1-microparticles or liraglutide-microparticles. Microparticles-loaded hGLP1 shows equivalent in vivo pharmacologic activity to the microparticles-loaded liraglutide.
Acknowledgements
The authors thank Thayna Sisnande, Dayana Cabral and Celimar Sinesia for helpful assistance with in vivo assays, to Dr. Sergio Luiz Cordeiro (CENABIO-UFRJ), Prof. Marcos Lopes Dias (IMA, UFRJ), and Dr. Larissa Leite de Almeida Carvalho (EngePol, COPPE, UFRJ) for excellent technical support, and to Laboratory Hertha-Meyer (IBCCF, UFRJ), CENABIO (UFRJ), EngePol (UFRJ) and IMA (UFRJ) for providing access to their analytical facilities.
Disclosure statement
The authors have no financial conflicts of interest with the contents of this article. LMTRL is a participant in patent applications by the UFRJ on controlled release of peptides unrelated to the present work.
Author contributions
LPI, FGSJ, and LMTRL conceived and designed the experiments. LPI, FGSJ, and LMTRL performed the experiments. LPI, FGSJ, and LMTRL analysed the data. LPI, FGSJ, and LMTRL contributed reagents/materials/analysis tools. LPI, FGSJ, and LMTRL wrote the manuscript.