Nano Research

Article Title

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


ApoE-derived peptide, lung administration, nanoparticles, Alzheimer’s disease, liposomes


Treatment options for Alzheimer’s disease (AD) are limited because of theinability of drugs to cross the blood–brain barrier (BBB). A promising strategyto overcome this obstacle is the use of nanoparticles (NPs). Previously, weshowed that intraperitoneal administration of liposomes functionalized withphosphatidic acid and an ApoE-derived peptide (mApoE-PA-LIP) reducesbrain beta-amyloid (Aβ) burden and ameliorates impaired memory in AD mice.Here, we investigated lung administration as an alternative, non-invasive NPdelivery route for reaching the brain. Our results show that mApoE-PA-LIPwere 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 g PA/g brain) followingin vivo intratracheal instillations. Lung administration of mApoE-PA-LIP toAD mice significantly decreased total brain Aβ (–60%; p < 0.05) compared tountreated mice. These results suggest that pulmonary administration could beexploited for brain delivery of NPs designed for AD therapy.

Graphical Abstract


Tsinghua University Press