Pulmonary administration of functionalized nanoparticles significantly reduces beta-amyloid in the brain of an Alzheimer＇s disease murine model  

作　　者：Giulio Sancini Roberta Dal Magro Francesca Ornaghi Claudia Balducci Gianluigi Forloni Marco Gobbi Mario Salmona Francesca Re 

机构地区：[1]Nanomedicine Center, School of Medicine and Surgery, University of Milano-Bicocca, via Cadore 48, 20900 Monza (MB), Italy [2]Department ofNeuroscience, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20159 Milano, Italy [3]Department of Biochemistry and Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, via La Masa 19, 20159 Milano, Italy

出　　处：《Nano Research》2016年第7期2190-2201,共12页纳米研究（英文版）

摘　　要：Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NPs）. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide （mApoE-PA-LIP） reduces brain beta-amyloid （A） burden and ameliorates impaired memory in AD mice. Here, we investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium （[C]-PA permeability = 6.5 ＋ 2.0 × 10^4 cm/min） in vitro and reach the brain （up to 0.6 μg PA/g brain） following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ （-60%; p 〈 0.05） compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NPs designed for AD therapy.Treatment options for Alzheimer＇s disease （AD） are limited because of the inability of drugs to cross the blood-brain barrier （BBB）. A promising strategy to overcome this obstacle is the use of nanoparticles （NPs）. Previously, we showed that intraperitoneal administration of liposomes functionalized with phosphatidic acid and an ApoE-derived peptide （mApoE-PA-LIP） reduces brain beta-amyloid （A） burden and ameliorates impaired memory in AD mice. Here, we investigated lung administration as an alternative, non-invasive NP delivery route for reaching the brain. Our results show that mApoE-PA-LIP were able to cross the pulmonary epithelium （[C]-PA permeability = 6.5 ＋ 2.0 × 10^4 cm/min） in vitro and reach the brain （up to 0.6 μg PA/g brain） following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreased total brain Aβ （-60%; p 〈 0.05） compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of NPs designed for AD therapy.

关 键 词：ApoE-derived peptide lung administration NANOPARTICLES Alzheimer＇s disease liposomes 

分 类 号：TQ463.54[化学工程—制药化工] Q421[生物学—神经生物学]