Sustained release and pharmacologic evaluation of human glucagon-like peptide-1 and liraglutide from polymeric microparticles

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.

Keywords:

• Glucagon-like peptide-1
• GLP1
• liraglutide
• microparticles
• long-acting release

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.

Additional information

Funding

This work was supported by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Finance Code #001), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro Carlos Chagas Filho (FAPERJ) and Programa Nacional de Apoio ao Desenvolvimento da Metrologia, Qualidade e Tecnologia (PRONAMETRO, to LMTRL) from the Instituto Nacional de Metrologia, Qualidade e Tecnologia (INMETRO). The funding agencies had no role in the study design, data collection and analysis, or decision to publish or prepare of the manuscript.