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.
Tsinghua University Press
Giulio Sancini,Roberta Dal Magro,Francesca Ornaghi,Claudia Balducci,Gianluigi Forloni,Marco Gobbi,Mario Salmona,Francesca Re, Pulmonary administration of functionalized nanoparticles significantly reduces beta-amyloid in the brain of an Alzheimer’s disease murine model. NanoRes.2016, 9(7): 2190–2201