4.8 Review

Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases

Journal

JOURNAL OF CONTROLLED RELEASE
Volume 235, Issue -, Pages 34-47

Publisher

ELSEVIER
DOI: 10.1016/j.jconrel.2016.05.044

Keywords

Blood-brain barrier; Nanoparticles; Stroke; Alzheimer's disease; Parkinson's disease; Brain repair

Funding

  1. Fundacao para a Ciencia e a Tecnologia (FCT) [PTDC/SAU-TOX/121887/2010, PTDC/BIM-MED/1118/2012, EXPL/BIM-MED/0822/2013, SFRH/BD/90365/2012, SFRH/BD/51678/2011, SFRH/BPD/94228/2013, SFRH/BD/79526/2011]
  2. European Community (ERC-StG) [307384]
  3. L'Oreal-UNESCO Portugal for Women in Science
  4. FEDER (QREN) through Programa Mais Centro
  5. COMPETE [PEst-C/SAU/UI0709/2011]
  6. Project Stem cell-based platforms for Regenerative and Therapeutic Medicine [Centro-07-ST24-FEDER-002008]
  7. European Research Council (ERC) [307384] Funding Source: European Research Council (ERC)
  8. Fundação para a Ciência e a Tecnologia [EXPL/BIM-MED/0822/2013, PTDC/BIM-MED/1118/2012, PTDC/SAU-TOX/121887/2010, SFRH/BD/79526/2011, SFRH/BD/90365/2012, SFRH/BD/51678/2011] Funding Source: FCT

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The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.

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