TY - JOUR

T1 - Multiple Protective Roles of Nanoliposome-Incorporated Baicalein against Alpha-Synuclein Aggregates

AU - Aliakbari, Farhang

AU - Mohammad-Beigi, Hossein

AU - Abbasi, Shahsanam

AU - Rezaei-Ghaleh, Nasrollah

AU - Lermyte, Frederik

AU - Parsafar, Soha

AU - Becker, Stefan

AU - Tafreshi, Azita Parvaneh

AU - O'Connor, Peter B.

AU - Collingwood, Joanna F.

AU - Christiansen, Gunna

AU - Sutherland, Duncan S.

AU - Jensen, Poul Henning

AU - Morshedi, Dina

AU - Otzen, Daniel E.

N1 - Publisher Copyright: © 2020 The Authors. Advanced Functional Materials published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2/10

Y1 - 2021/2/10

N2 - 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.

AB - 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.

KW - baicalein

KW - fibrillation

KW - neurotoxicity

KW - Parkinson's disease

KW - zwitterionic nanoliposomes

KW - α-synuclein

UR - http://www.scopus.com/inward/record.url?scp=85096803173&partnerID=8YFLogxK

U2 - 10.1002/adfm.202007765

DO - 10.1002/adfm.202007765

M3 - Journal article

AN - SCOPUS:85096803173

VL - 31

JO - Advanced Functional Materials

JF - Advanced Functional Materials

SN - 1616-301X

IS - 7

M1 - 2007765

ER -