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Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

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DOI

  • Farhang Aliakbari, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Hossein Mohammad-Beigi
  • ,
  • Shahsanam Abbasi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Nasrollah Rezaei-Ghaleh, University of Göttingen
  • ,
  • Frederik Lermyte, University of Warwick
  • ,
  • Soha Parsafar, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Stefan Becker, Max Planck Institute for Biophysical Chemistry (Karl Friedrich Bonhoeffer Institute)
  • ,
  • Azita Parvaneh Tafreshi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Peter B. O'Connor, University of Warwick
  • ,
  • Joanna F. Collingwood, University of Warwick
  • ,
  • Gunna Christiansen
  • ,
  • Duncan S. Sutherland
  • Poul Henning Jensen
  • Dina Morshedi, National Institute for Genetic Engineering and Biotechnology Iran
  • ,
  • Daniel E. Otzen

Nanoparticles are useful for increasing drug stability, solubility, and availability. The small molecule baicalein inhibits fibrillation, and detoxifies aggregates of α-synuclein (αSN) associated with Parkinson's disease (PD), but it suffers from instability, low solubility and consequent low availability. Here it is demonstrated that incorporation of baicalein into zwitterionic nanoliposomes (NLP-Ba) addresses these problems. NLP-Ba inhibits αSN fibril initiation, elongation, secondary nucleation, and also depolymerizes mature fibrils more effectively than free baicalein and prevents soluble αSN aggregates from seeding new fibrils. Importantly, NLP-Ba perturbs oligomers’ capacity to permeabilize the membrane. The interaction between NLP-Ba and αSN is confirmed by different biophysical techniques. This nanosystem crosses the blood-brain barrier in vitro and is effective against rotenone neurotoxicity in vivo. The effect of NLP-Ba on αSN fibrillation/cytotoxicity is attributed to a combination of free baicalein and empty NLPs. The results indicate a neuroprotective role for NLP-Ba in decreasing αSN pathogenicity in PD and highlight the use of nanoliposomes to mobilize poorly soluble hydrophobic drugs.

Original languageEnglish
Article number2007765
JournalAdvanced Functional Materials
Volume31
Issue7
ISSN1616-301X
DOIs
Publication statusPublished - 10 Feb 2021

Bibliographical note

Publisher Copyright:
© 2020 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

    Research areas

  • baicalein, fibrillation, neurotoxicity, Parkinson's disease, zwitterionic nanoliposomes, α-synuclein

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