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Nano Research

, Volume 9, Issue 7, pp 2190–2201 | Cite as

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

  • Giulio Sancini
  • Roberta Dal MagroEmail author
  • Francesca Ornaghi
  • Claudia Balducci
  • Gianluigi Forloni
  • Marco Gobbi
  • Mario Salmona
  • Francesca Re
Research Article

Abstract

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.

Keywords

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

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Copyright information

© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Giulio Sancini
    • 1
  • Roberta Dal Magro
    • 1
    Email author
  • Francesca Ornaghi
    • 1
  • Claudia Balducci
    • 2
  • Gianluigi Forloni
    • 2
  • Marco Gobbi
    • 3
  • Mario Salmona
    • 3
  • Francesca Re
    • 1
  1. 1.Nanomedicine Center, School of Medicine and SurgeryUniversity of Milano-BicoccaMonza (MB)Italy
  2. 2.Department of NeuroscienceIRCCS-Istituto di Ricerche Farmacologiche Mario NegriMilanoItaly
  3. 3.Department of Biochemistry and Molecular PharmacologyIRCCS-Istituto di Ricerche Farmacologiche Mario NegriMilanoItaly

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