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Quercetin-biapigenin nanoparticles are effective to penetrate the blood–brain barrier

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Abstract

Search for efficient therapeutic agents for central nervous system (CNS) disorders has been extensive. Nevertheless, blood–brain barrier (BBB) is an obstacle that prevents the majority of compounds to act in these diseases. It is, thus, of extreme relevance the BBB overcome, in order to deliver a drugs therapeutically active concentration to the action site, with the least losses and interaction with other organs, tissues, or cells. The present study aimed to investigate the potential protective effect of quercetin-biapigenin encapsulated into poly(Ɛ-polycaprolactone) (PCL) nanoparticles against t-BOOH-induced oxidative stress in several brain cell lines, as well as evaluate the permeability of those active molecules through an in vitro BBB model. The three cell lines under study (BV-2, hcmec/D3, and U87) presented different reactions to t-BOOH. In general, quercetin-biapigenin PCL-loaded nanoparticles were able to minimize compound toxicity they convey, regardless the cell line. Quercetin-biapigenin PCL-loaded nanoparticles (Papp of approximately 80 × 10–6 cm/s) revealed to be more permeable than free compounds (Papp of approximately 50 × 10–6 cm/s). As of our knowledge, this is the first report of quercetin-biapigenin PCL-loaded nanoparticle activity in brain cells. It is also the first determining its permeability through BBB, as an effective nanocarrier for brain delivery

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Funding

This paper was financed by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” UID/BIM/04293/2019. It was also supported by the “Contrato-Programa” UIDB/04050/2020 funded by national funds through the FCT I.P. Ana Isabel Oliveira was supported by Escola Superior de Saúde do Porto and Instituto Politécnico do Porto (Programa de Formação Avançada de Docentes).

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Authors and Affiliations

  1. Centro de Investigação Em Saúde E Ambiente (CISA), Escola Superior de Saúde –Politécnico do Porto (ESS-P.Porto), 4000-072, Porto, Portugal

    Ana Isabel Oliveira & Cláudia Pinho

  2. i3S - Instituto de Investigação E Inovação Em Saúde, Universidade Do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal

    Bruno Sarmento

  3. INEB - Instituto Nacional de Engenharia Biomédica, Universidade Do Porto, Rua Alfredo Allen 208, 4200-135, Porto, Portugal

    Bruno Sarmento

  4. CESPU, Instituto de Investigação E Formação Avançada Em Ciências E Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, 4585-116, Gandra, Portugal

    Bruno Sarmento

  5. Centre of Molecular and Environmental Biology (CBMA), Biology Department, Department of Biology, University of Minho, 4710-057, Braga, Portugal

    Alberto C. P. Dias

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  1. Ana Isabel Oliveira
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  2. Cláudia Pinho
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  4. Alberto C. P. Dias
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Contributions

As for different contributions for this manuscript, Ana Isabel Oliveira had intervention in all the practical parts of the study and on the elaboration of the paper. Cláudia Pinho intervened on specific parts of the study (cell line assays) aiding on the elaboration of the paper on those specific parts. Bruno Sarmento and Alberto Dias intervened on the structure and elaboration of the article and review it. All authors have knowledge and approve the final version of the manuscript.

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Correspondence to Ana Isabel Oliveira.

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Oliveira, A.I., Pinho, C., Sarmento, B. et al. Quercetin-biapigenin nanoparticles are effective to penetrate the blood–brain barrier. Drug Deliv. and Transl. Res. 12, 267–281 (2022). https://doi.org/10.1007/s13346-021-00917-6

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