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

Farhang Aliakbari, Hossein Mohammad-Beigi, Shahsanam Abbasi, Nasrollah Rezaei-Ghaleh, Frederik Lermyte, Soha Parsafar, Stefan Becker, Azita Parvaneh Tafreshi, Peter B. O'Connor, Joanna F. Collingwood, Gunna Christiansen, Duncan S. Sutherland, Poul Henning Jensen, Dina Morshedi, Daniel E. Otzen*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Abstract

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

Keywords

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

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