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      Physiological and Pathological Factors Affecting Drug Delivery to the Brain by Nanoparticles

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          Abstract

          The prevalence of neurological/neurodegenerative diseases, such as Alzheimer's disease is known to be increasing due to an aging population and is anticipated to further grow in the decades ahead. The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. An increasingly important observation is that the physiology of the brain alters during many brain diseases, and aging adds even more to the complexity of the disease. There is a notion that the permeability of the blood–brain barrier (BBB) increases with aging or disease, however, the body has a defense mechanism that still retains the separation of the brain from harmful chemicals in the blood. This makes drug delivery to the diseased brain, even more challenging and complex task. Here, the physiological changes to the diseased brain and aged brain are covered in the context of drug delivery to the brain using nanoparticles. Also, recent and novel approaches are discussed for the delivery of therapeutic agents to the diseased brain using nanoparticle based or magnetic resonance imaging guided systems. Furthermore, the complement activation, toxicity, and immunogenicity of brain targeting nanoparticles as well as novel in vitro BBB models are discussed.

          Abstract

          The treatment of brain diseases is challenging partly due to the inaccessibility of therapeutic agents to the brain. The physiology of the brain alters during neurological diseases, making treatment challenging. Nanoparticles are novel method of drug delivery, however, an understanding of biological responses such as immunogenicity and toxicity is essential for safe application.

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          Most cited references10

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          Characterization of Nanoparticles Intended for Drug Delivery

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            Handbook of clinical neurology

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              Nanotechnology-based targeted drug delivery systems for brain tumors

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                Author and article information

                Contributors
                t.ehtezazi@ljmu.ac.uk
                Journal
                Adv Sci (Weinh)
                Adv Sci (Weinh)
                10.1002/(ISSN)2198-3844
                ADVS
                Advanced Science
                John Wiley and Sons Inc. (Hoboken )
                2198-3844
                15 March 2021
                June 2021
                : 8
                : 11 ( doiID: 10.1002/advs.v8.11 )
                : 2002085
                Affiliations
                [ 1 ] School of Pharmacy and Biomolecular Sciences Liverpool John Moores University Byrom Street Liverpool L3 3AF UK
                [ 2 ] Division of Pharmacy and Optometry The University of Manchester Stopford Building, Oxford Road Manchester M13 9PT UK
                [ 3 ] Cambridge Innovation Technologies Consulting (CITC) Limited St. John's Innovation Centre Cowley Road Cambridge CB4 0WS UK
                [ 4 ] Department of Clinical Neurosciences Clifford Allbutt Building – Cambridge Biosciences Campus and NIHR Biomedical Research Centre University of Cambridge Hills Road Cambridge CB2 0HA UK
                [ 5 ] School of Engineering and Physical Sciences Heriot‐Watt University William Perkin Building Edinburgh EH14 4AS UK
                [ 6 ] Department of Haematology Peterborough City Hospital Edith Cavell Campus Bretton Gate Peterborough Peterborough PE3 9GZ UK
                [ 7 ] Institute for Research in Biomedicine (IRB Barcelona) Barcelona Institute of Science and Technology (BIST) Baldiri Reixac 10 Barcelona 08028 Spain
                Author notes
                [*] [* ]E‐mail:t.ehtezazi@ljmu.ac.uk

                Author information
                https://orcid.org/0000-0002-1576-2396
                Article
                ADVS2439
                10.1002/advs.202002085
                8188209
                34105297
                bd9bcad7-e3c8-4abc-999d-a7ce13615959
                © 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 January 2021
                : 03 June 2020
                Page count
                Figures: 18, Tables: 8, Pages: 45, Words: 38010
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                June 9, 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.2 mode:remove_FC converted:09.06.2021

                aging brain,blood–brain barrier model,complement activation,drug delivery to the brain,immunogenicity,nanoparticles,neurodegenerative diseases

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