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Preparation, characterization and in vitro evaluation of chitosan nanoparticles for the oral delivery of GLP-1 analog liraglutide

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Abstract

Liraglutide (LIRA) is a GLP-1 analog peptide used for the treatment of type 2 diabetes. Owing to its degradation in the gastrointestinal tract, LIRA is administered via subcutaneous injection. Oral delivery of peptides is a challenge; however, nanotechnology can be an effective strategy against such challenges. In this study, chitosan nanoparticles were developed and characterized as alternative carriers for oral LIRA administration. Nanoparticles were prepared via ionotropic gelation using sodium tripolyphosphate as a cross-linking agent. Chitosan nanoparticles showed spherical shape, mean diameter of 323 nm, polydispersity index of 0.453, zeta potential of + 23.4 mV, as well as 24% encapsulation efficiency. Physicochemical characterization revealed the interaction of LIRA with nanoparticles and its amorphization after nanoencapsulation. In vitro release analysis showed that approximately 34.7% of LIRA was released during 102 h through an anomalous process, making the Baker–Lonsdale model the best fit for the release kinetics. Chitosan nanoparticles protected more than 80% LIRA from degradation in simulated gastric and intestinal fluids and showed be mucoadhesive. Overall of results demonstrated the potential application of chitosan nanoparticles in the oral delivery of LIRA.

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Acknowledgements

The authors thank to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-Brazil—0001) for the scholarship for J. Ziebarth, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil, proc. 429728/2018-2) and Financiadora de Projetos e Estudos (FINEP-Brazil) for partial financial support.

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  1. Programa de Pós-Graduação em Química, Universidade Estadual do Centro-Oeste/UNICENTRO, Guarapuava, PR, Brazil

    Jeferson Ziebarth & Rubiana Mara Mainardes

  2. Departamento de Farmácia, Laboratório de Nanotecnologia Farmacêutica, Universidade Estadual do Centro-Oeste/UNICENTRO, Alameda Élio Antonio Dalla Vecchia, 838, Guarapuava, PR, CEP 85040-167, Brazil

    Rubiana Mara Mainardes

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RMM contributed to the study conception and design. Material preparation, data collection and analysis were performed by JZ. The first draft of the manuscript was written by JZ and revised by RMM. All authors read and approved the final manuscript.

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Correspondence to Rubiana Mara Mainardes.

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Ziebarth, J., Mainardes, R.M. Preparation, characterization and in vitro evaluation of chitosan nanoparticles for the oral delivery of GLP-1 analog liraglutide. J Therm Anal Calorim 148, 2443–2455 (2023). https://doi.org/10.1007/s10973-022-11909-0

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