Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates

被引:120
作者
Barbara, Ruozi [1 ]
Belletti, Daniela [1 ]
Pederzoli, Francesca [1 ]
Masoni, Martina [1 ]
Keller, Johannes [2 ]
Ballestrazzi, Antonio [5 ]
Vandelli, Maria Angela [1 ]
Tosi, Giovanni [1 ]
Grabrucker, Andreas M. [2 ,3 ,4 ]
机构
[1] Univ Modena & Reggio Emilia, Dept Life Sci, Via Campi 103, Modena, Italy
[2] Ulm Univ, Neurol Dept, Neuroctr, WG Mol Anal Synaptopathies, Ulm, Germany
[3] Ulm Univ, Inst Anat & Cell Biol, Ulm, Germany
[4] Univ Limerick, Dept Biol Sci, V95PH61, Limerick, Ireland
[5] Univ Modena & Reggio Emilia, Dept Phys Sci Informat & Math, Modena, Italy
关键词
Synapse; Amyloid; Alzheimer's disease; BBB targeting nanoparticles; Nanotechnology; Curcumin; CENTRAL-NERVOUS-SYSTEM; PLGA NANOPARTICLES; POLYMERIC NANOPARTICLES; ALZHEIMERS-DISEASE; DRUG-DELIVERY; SIALIC-ACID; PROTEIN; MECHANISMS; NEUROPATHOLOGY; OLIGOMERS;
D O I
10.1016/j.ijpharm.2017.05.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The formation of extracellular aggregates built up by deposits of beta-amyloid (A beta) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to display anti-amyloidogenic activity, not only by inhibiting the formation of new A beta aggregates, but also by disaggregating existing ones. However, the uptake of Curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of Curcumin into the brain are highly desired. Here, we encapsulated Curcumin as active ingredient in PLGA (polylactide-co-glycolic-acid) nano particles (NPs), modified with g7 ligand for BBB crossing. We performed in depth analyses of possible toxicity of these NPs, uptake, and, foremost, their ability to influence A beta pathology in vitro using primary hippocampal cell cultures. Our results show no apparent toxicity of the formulated NPs, but a significant decrease of A beta aggregates in response to Curcumin loaded NPs. We thus conclude that brain delivery of Curcumin using BBB crossing NPs is a promising future approach in the treatment of AD. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:413 / 424
页数:12
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