title: Targeted Nanoparticles for the Treatment of Alzheimer's Disease.
abstract: Alzheimer's disease (AD) has a dramatic impact on society. The therapeutic targets are located in the central nervous system (CNS), which limits the efficacy of drugs systemically administered: the blood-brain barrier (BBB) selectively allows the permeation of just a few kinds of molecules from the systemic circulation to the CNS. On the other hand, local administration routes to CNS are highly invasive.
  
  
  
  In this article, we have reviewed therapeutic approaches against AD, which are based on nanoparticles targeted to the brain and to the pathological hallmarks of the disease. The existing literature has been classified according to the AD feature that is addressed.
  
  
  
  Nanoparticles have been used for the targeted delivery of drugs aiming to reduce the AD symptoms or to reverse the course of the disease. For this task the multivalency of nanoparticles has allowed their functionalization with several kinds of targeting groups, to cross the BBB and to target the place of treatment. With this approach an increased drug bioavailability has been achieved in the CNS using intravenous administration in place of more invasive administration routes. Additionally, nanoparticles have also been used in the development of vaccines and therapeutic formulations for intranasal administration.
  
  
  
  Targeted nanoparticles have been proved useful to enhance the performance of therapies against AD in animal models. A better understanding of AD mechanisms will help the successful application of targeted nanoparticles for combined therapies.
authors.affiliation: Instituto de Nanociencia de Aragón (INA) Universidad de Zaragoza, Edificio I+D, 50018 Zaragoza, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Martín-Rapun
authors.affiliation: Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, 50018-Zaragoza,, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: De Matteis
authors.affiliation: Instituto de Ciencia de Materiales de Aragón-CSIC/Universidad de Zaragoza and CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Ambrosone
authors.affiliation: Instituto de Ciencia de Materiales de Aragón-CSIC/Universidad de Zaragoza and CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Garcia-Embid
authors.affiliation: Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, 50018-Zaragoza, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gutierrez
authors.affiliation: Instituto de Ciencia de Materiales de Aragón-CSIC/Universidad de Zaragoza, and CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Zaragoza, Spain.
authors.forename: Jesus M
authors.initials: JM
authors.lastname: de la Fuente
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*
keywords: Alzheimer's disease; blood-brain barrier (BBB); central nervous system (CNS); drug delivery; nanoparticles; neurodegeneration; targeted medicine