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 （NP...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.展开更多
文摘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.
