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A Novel Bioresorbable Device as a Controlled Release System for Protecting Cells from Oxidative Stress from Alzheimer’s Disease

Molecular Neurobiology volume 54, pages 6827–6838 (2017)Cite this article

Abstract

Bioresorbable electrospun fibres have highly functional features that can preserve drug efficacy, avoiding premature degradation, and control drug release rates over long periods. In parallel, it is known that Alzheimer’s disease (AD) has been linked to impaired insulin signalling in the brain. Glucagon-like peptide 1 (GLP-1) analogues have beneficial effects on insulin release and possess exceptional neuroprotective properties. Herein, we describe for the first time the incorporation of a GLP-1 analogue, liraglutide, into electrospun poly (lactic acid) (PLA) fibres with in situ gelatin capsules, in order to provide the controlled release of liraglutide, improving neuroprotective properties. In this study, PLA, a bioresorbable polymer in which degradation products have neurogenesis characteristics, was electrospun and loaded with liraglutide. Moreover, PLA/liraglutide fibres were encapsulated with gelatin and were shown to have better properties than the non-encapsulated fibres in terms of the controlled release of liraglutide, which was accomplished in the present study for up to 60 days. We observed that this biodevice was completely encapsulated with gelatin, which made the material more hydrophilic than PLA fibres alone and the biodevice was able to enhance fibroblast interaction and reduce mitochondrial stress in a neuroblastoma cell line. In this manner, this study introduces a new material which can improve neuroprotective properties from AD oxidative stress via the sustained long-lasting release of liraglutide.

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Acknowledgments

The authors would like to thank the São Paulo Research Foundation (FAPESP, AOL: grant 2011/17877-7 and BPE 2015/09697-0; FRM: grant 2011/20345-7 and BPE 2016/00575-1), the National Council for Scientific and Technological Development (CNPq, 474090/2013-2), the Brazilian Innovation Agency (FINEP–grant 0113042800) and the Coordination for the Improvement of Higher Education Personnel (CAPES, grant 88887.095044/2015-00). G. N. Salles would also like to thank FAPESP for the PhD scholarship (2014/20561-0). The authors would like to acknowledge Prof. Fabio Klamt who provided the SH-SY5Y cells.

Authors’ Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

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Authors and Affiliations

  1. Laboratory of Biomedical Nanotechnology, Institute of Research and Development (IP&D), University of Vale do Paraiba (UNIVAP), São Jose dos Campos, São Paulo, 12244-000, Brazil

    Geisa Nogueira Salles, Fernanda Aparecida dos Santos Pereira, Fernanda Roberta Marciano & Anderson Oliveira Lobo

  2. Laboratory of Dynamics of Cellular Compartments, IP&D, University of Vale do Paraíba (Univap), São Jose dos Campos, São Paulo, 12244-000, Brazil

    Geisa Nogueira Salles, Fernanda Aparecida dos Santos Pereira & Cristina Pacheco-Soares

  3. Department of Medicine, Biomaterials Innovation Research Center, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, MA, 02139, USA

    Fernanda Roberta Marciano & Anderson Oliveira Lobo

  4. Department of Chemical Engineering, Northeastern University, Boston, MA, 02115, USA

    Fernanda Roberta Marciano, Thomas J Webster & Anderson Oliveira Lobo

  5. Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YQ, England

    Christian Hölscher

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  1. Geisa Nogueira Salles
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  2. Fernanda Aparecida dos Santos Pereira
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Correspondence to Anderson Oliveira Lobo.

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Salles, G.N., Pereira, F.A.d.S., Pacheco-Soares, C. et al. A Novel Bioresorbable Device as a Controlled Release System for Protecting Cells from Oxidative Stress from Alzheimer’s Disease. Mol Neurobiol 54, 6827–6838 (2017). https://doi.org/10.1007/s12035-016-0200-0

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