From the lungs to the brain: the fantastic voyage of nanoparticles targeting beta-amyloid

The brain is always confronted with the dilemma of the protection from noxious substances from the blood and the delivery of vital metabolites. Endothelial cells, forming together with other cells the blood-brain barrier (BBB), are known as the “gatekeepers” of this trafficking. Recent applications in nanomedicine focus on nanoparticles and liposomes as they are promising tools for site-specific delivery of drugs and diagnostic agents, through the possibility to functionalize their surface with target-specific ligands. Treatment options for Alzheimer’s disease (AD) are limited because of the inability of drugs to cross the BBB. We disclosed 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. Among the different administration routes, pulmonary delivery is a field of increasing interest not only for the local treatment of airway diseases but also for the systemic administration. Here we prove that mApoE-PA-LIP are able to cross the pulmonary epithelium in vitro and reach the brain following in vivo intratracheal instillations. Lung administration of mApoE-PA-LIP to AD mice significantly decreases total brain Aβ (–60%; p < 0.05) compared to untreated mice. These results suggest that pulmonary administration could be exploited for brain delivery of nanoparticles designed for AD therapy.