title: Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.
abstract: 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.
authors.affiliation: Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Saraiva
authors.affiliation: Biocant - Center of Innovation in Biotechnology, 3060-197 Cantanhede, Portugal; Programme in Experimental Biology and Biomedicine (PDBEB), Center for Neuroscience and Cell Biology, 3004-504 Coimbra, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal; Science Faculty Jean Perrin, University of Artois, Lens, France.
authors.forename: Catarina
authors.initials: C
authors.lastname: Praça
authors.affiliation: Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal.
authors.forename: Tiago
authors.initials: T
authors.lastname: Santos
authors.affiliation: Biocant - Center of Innovation in Biotechnology, 3060-197 Cantanhede, Portugal; Institute for Interdisciplinary Research, University of Coimbra (IIIUC), 3030-789 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, 3004-504 Coimbra, Portugal. Electronic address: lino@biocant.pt.
authors.forename: Lino
authors.initials: L
authors.lastname: Ferreira
authors.affiliation: Health Sciences Research Centre, Faculty of Health Sciences, University of Beira Interior, 6200-506 Covilhã, Portugal. Electronic address: libernardino@gmail.com.
authors.forename: Liliana
authors.initials: L
authors.lastname: Bernardino
mesh_terms: D000818:Animals; D001692:Biological Transport; D001921:Brain / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage* / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism*
keywords: Alzheimer's disease; Blood–brain barrier; Brain repair; Nanoparticles; Parkinson's disease; Stroke