Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease

Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, e...

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Main Authors: Shengnuo Fan, Yuqiu Zheng, Xuan Liu, Wenli Fang, Xiaoyu Chen, Wang Liao, Xiuna Jing, Ming Lei, Enxiang Tao, Qiulan Ma, Xingmei Zhang, Rui Guo, Jun Liu
Format: Article
Language:English
Published: Taylor & Francis Group 2018-01-01
Series:Drug Delivery
Subjects:
Online Access:http://dx.doi.org/10.1080/10717544.2018.1461955
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author Shengnuo Fan
Yuqiu Zheng
Xuan Liu
Wenli Fang
Xiaoyu Chen
Wang Liao
Xiuna Jing
Ming Lei
Enxiang Tao
Qiulan Ma
Xingmei Zhang
Rui Guo
Jun Liu
author_facet Shengnuo Fan
Yuqiu Zheng
Xuan Liu
Wenli Fang
Xiaoyu Chen
Wang Liao
Xiuna Jing
Ming Lei
Enxiang Tao
Qiulan Ma
Xingmei Zhang
Rui Guo
Jun Liu
author_sort Shengnuo Fan
collection DOAJ
description Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.
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spelling doaj.art-5a8568acd3c64032a59acc48899309942022-12-22T01:46:37ZengTaylor & Francis GroupDrug Delivery1071-75441521-04642018-01-012511091110210.1080/10717544.2018.14619551461955Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s diseaseShengnuo Fan0Yuqiu Zheng1Xuan Liu2Wenli Fang3Xiaoyu Chen4Wang Liao5Xiuna Jing6Ming Lei7Enxiang Tao8Qiulan Ma9Xingmei Zhang10Rui Guo11Jun Liu12Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversityJinan UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversityUniversity of CaliforniaKarolinska Institute, Center for Molecular Medicine, Karolinska University Hospital at SolnaJinan UniversitySun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAlzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.http://dx.doi.org/10.1080/10717544.2018.1461955curcuminb6 peptidenanoparticlesblood compatibilityalzheimer’s disease
spellingShingle Shengnuo Fan
Yuqiu Zheng
Xuan Liu
Wenli Fang
Xiaoyu Chen
Wang Liao
Xiuna Jing
Ming Lei
Enxiang Tao
Qiulan Ma
Xingmei Zhang
Rui Guo
Jun Liu
Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
Drug Delivery
curcumin
b6 peptide
nanoparticles
blood compatibility
alzheimer’s disease
title Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
title_full Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
title_fullStr Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
title_full_unstemmed Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
title_short Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential use in Alzheimer’s disease
title_sort curcumin loaded plga peg nanoparticles conjugated with b6 peptide for potential use in alzheimer s disease
topic curcumin
b6 peptide
nanoparticles
blood compatibility
alzheimer’s disease
url http://dx.doi.org/10.1080/10717544.2018.1461955
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