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

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 (Aβ) 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 ([14C]-PA permeability = 6.5 ± 2.0 × 10–6 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. [Figure not available: see fulltext.]