新型载姜黄素纳米颗粒经设计可穿越血脑屏障并能破坏β-淀粉样蛋白聚集体。
Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates.
作者信息
Barbara Ruozi, Belletti Daniela, Pederzoli Francesca, Masoni Martina, Keller Johannes, Ballestrazzi Antonio, Vandelli Maria Angela, Tosi Giovanni, Grabrucker Andreas M
机构信息
Department of Life Sciences, University of Modena and Reggio Emilia, Italy.
WG Molecular Analysis of Synaptopathies, Neurology Dept., Neurocenter of Ulm University, Ulm, Germany.
出版信息
Int J Pharm. 2017 Jun 30;526(1-2):413-424. doi: 10.1016/j.ijpharm.2017.05.015. Epub 2017 May 8.
The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) 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 Aβ 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) nanoparticles (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 Aβ pathology in vitro using primary hippocampal cell cultures. Our results show no apparent toxicity of the formulated NPs, but a significant decrease of Aβ 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.
由β-淀粉样蛋白(Aβ)沉积物形成的细胞外聚集体是阿尔茨海默病(AD)的一个标志。据报道,姜黄素不仅通过抑制新的Aβ聚集体的形成,还通过分解现有的聚集体来显示抗淀粉样蛋白生成活性。然而,姜黄素进入大脑的能力因其穿过血脑屏障(BBB)的能力较低而受到严重限制。因此,非常需要将姜黄素靶向递送至大脑的新策略。在这里,我们将姜黄素作为活性成分封装在聚乳酸-乙醇酸共聚物(PLGA)纳米颗粒(NPs)中,并用g7配体进行修饰以穿过血脑屏障。我们对这些纳米颗粒的潜在毒性、摄取情况进行了深入分析,最重要的是,使用原代海马细胞培养物在体外分析了它们影响Aβ病理的能力。我们的结果表明,所制备的纳米颗粒没有明显的毒性,但载有姜黄素的纳米颗粒可使Aβ聚集体显著减少。因此,我们得出结论,使用可穿过血脑屏障的纳米颗粒将姜黄素递送至大脑是未来治疗AD的一种有前景的方法。