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

Drug Delivery

Xingmei Zhang¹  Shengnuo Fan²  Enxiang Tao²  Wenli Fang²  Wang Liao²  Yuqiu Zheng²  Xiuna Jing²  Ming Lei²  Jun Liu³  Xiaoyu Chen⁴  Qiulan Ma⁵  Xuan Liu⁶  Rui Guo⁶ 

[1] Applied Immunology and Immunotherapy, Department of Clinical Neuroscience, Karolinska Institute, Center for Molecular Medicine, Karolinska University Hospital at Solna, Stockholm, Sweden;Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Chin;Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;Zhongshan City People’s Hospital, Zhongshan City, Guangdong Province, China;Department of Neurology, University of California, Los Angeles, CA, USA;Key Laboratory of Biomaterials of Guangdong Higher Education Institutes Department of Biomedical Engineering, Jinan University, Guangzhou, China;

关键词: Curcumin;    B6 peptide;    nanoparticles;    blood compatibility;    Alzheimer’s disease;   

DOI  :  10.1080/10717544.2018.1461955

来源: publisher

【 摘 要 】

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.

【 授权许可】

CC BY