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Increasing levels of insulin secretion in bioartificial pancreas technology: co-encapsulation of beta cells and nanoparticles containing GLP-1 in alginate hydrogels

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Abstract

The success of diabetes treatment with bioartificial pancreas is still hindered by a high rate of graft failure caused by poorly functioning cells. The incretin effect of glucagon like peptide-1 (GLP-1) make this peptide an attractive therapeutic agent to improve the success of transplantation of encapsulated beta cells. Our objective was to develop a novel model based on the co-encapsulation of beta cells with nanoparticles containing GLP-1 on alginate hydrogels, allowing its delivery and action in the specific target, beta cells. To this end, poly(lactide-co-glycolide) (PLGA) nanoparticles containing GLP-1 were prepared to be encapsulated together with INS-1E beta cells. Then, cells were encapsulated in alginate alone (Alg 0) and co-encapsulated with PLGA nanoparticles containing GLP-1 (Alg GLP-1). Hydrogels were maintained in culture during 7 days for evaluation of GLP-1’s influence in cellular performance, namely the crucial feature of insulin secretion. PLGA nanoparticles had an average size of 169.3 nm, a polydispersity index of 0.05 and an average zeta-potential of −24.3 mV. The average association efficiency of GLP-1 was 65.4% and the in vitro release test showed 71% of GLP-1 delivery after 7 days. Comparing the cellular conditions (Alg 0 and Alg GLP-1), the presence of nanoparticles led to increased cellular metabolic activity and 8-fold higher insulin levels. Our results reveal a promising successful role of GLP-1 nanoparticles in ensuring the viability of encapsulated beta cells in alginate hydrogel, by promoting its proper delivery and action. Further studies are needed to extensively characterize this new model of bioartifical pancreas.

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Acknowledgments

The present work is a collaboration between iCBR and INEB/i3S, supported by the Portuguese Foundation for Science and Technology: FCT Strategic Plan UID/NEU/04539/2013, UID/BIM/04293/2013 and SFRH/BD/72964/2010.

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Authors and Affiliations

  1. Laboratory of Physiology, iCBR - Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Pólo III - Azinhaga Santa Comba, Celas, 3000-548, Coimbra, Portugal

    Joana Crisóstomo & Raquel Seiça

  2. INEB - Instituto de Engenharia Biomédica, Porto, Portugal

    Francisca Araújo, Pedro Granja, Cristina Barrias & Bruno Sarmento

  3. i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal

    Francisca Araújo, Pedro Granja, Cristina Barrias & Bruno Sarmento

  4. FEUP - Faculdade de Engenharia, Universidade do Porto, Porto, Portugal

    Pedro Granja

  5. ICBAS - Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal

    Pedro Granja & Cristina Barrias

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  1. Joana Crisóstomo
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  2. Francisca Araújo
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  3. Pedro Granja
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  4. Cristina Barrias
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  5. Bruno Sarmento
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  6. Raquel Seiça
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Correspondence to Joana Crisóstomo.

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All authors comply to Springer’s ethical policies. The authors report no conflicts of interest in present work. This article does not contain any studies with human participants or animals performed by any of the authors.

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Crisóstomo, J., Araújo, F., Granja, P. et al. Increasing levels of insulin secretion in bioartificial pancreas technology: co-encapsulation of beta cells and nanoparticles containing GLP-1 in alginate hydrogels. Health Technol. 10, 885–890 (2020). https://doi.org/10.1007/s12553-020-00427-4

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  • DOI: https://doi.org/10.1007/s12553-020-00427-4

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