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      Blood-Brain Delivery Methods Using Nanotechnology

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          Abstract

          Pathologies of the brain, of which brain cancer, Alzheimer’s disease, Parkinson’s disease, stroke, and multiple sclerosis, are some of the most prevalent, and that presently are poorly treated due to the difficulties associated with drug development, administration, and targeting to the brain. The existence of the blood-brain barrier, a selective permeability system which acts as a local gateway against circulating foreign substances, represents the key challenge for the delivery of therapeutic agents to the brain. However, the development of nanotechnology-based approaches for brain delivery, such as nanoparticles, liposomes, dendrimers, micelles, and carbon nanotubes, might be the solution for improved brain therapies.

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          Blood-brain barrier: structural components and function under physiologic and pathologic conditions.

          Yuri Persidsky, Servio H. Ramirez, James Haorah … (2006)
          The blood-brain barrier (BBB) is the specialized system of brain microvascular endothelial cells (BMVEC) that shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream. The close interaction between BMVEC and other components of the neurovascular unit (astrocytes, pericytes, neurons, and basement membrane) ensures proper function of the central nervous system (CNS). Transport across the BBB is strictly limited through both physical (tight junctions) and metabolic barriers (enzymes, diverse transport systems). A functional polarity exists between the luminal and abluminal membrane surfaces of the BMVEC. As a result of restricted permeability, the BBB is a limiting factor for the delivery of therapeutic agents into the CNS. BBB breakdown or alterations in transport systems play an important role in the pathogenesis of many CNS diseases (HIV-1 encephalitis, Alzheimer's disease, ischemia, tumors, multiple sclerosis, and Parkinson's disease). Proinflammatory substances and specific disease-associated proteins often mediate such BBB dysfunction. Despite seemingly diverse underlying causes of BBB dysfunction, common intracellular pathways emerge for the regulation of the BBB structural and functional integrity. Better understanding of tight junction regulation and factors affecting transport systems will allow the development of therapeutics to improve the BBB function in health and disease.
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            Nose-to-brain drug delivery: An update on clinical challenges and progress towards approval of anti-Alzheimer drugs

            Amit Alexander, Swarnlata Saraf, Shailendra Saraf … (2018)
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              Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain.

              Mayur Patel, Bhoomika M. Patel (2017)
              CNS disorders are on the rise despite advancements in our understanding of their pathophysiological mechanisms. A major hurdle to the treatment of these disorders is the blood-brain barrier (BBB), which serves as an arduous janitor to protect the brain. Many drugs are being discovered for CNS disorders, which, however fail to enter the market because of their inability to cross the BBB. This is a pronounced challenge for the pharmaceutical fraternity. Hence, in addition to the discovery of novel entities and drug candidates, scientists are also developing new formulations of existing drugs for brain targeting. Several approaches have been investigated to allow therapeutics to cross the BBB. As the molecular structure of the BBB is better elucidated, several key approaches for brain targeting include physiological transport mechanisms such as adsorptive-mediated transcytosis, inhibition of active efflux pumps, receptor-mediated transport, cell-mediated endocytosis, and the use of peptide vectors. Drug-delivery approaches comprise delivery from microspheres, biodegradable wafers, and colloidal drug-carrier systems (e.g., liposomes, nanoparticles, nanogels, dendrimers, micelles, nanoemulsions, polymersomes, exosomes, and quantum dots). The current review discusses the latest advancements in these approaches, with a major focus on articles published in 2015 and 2016. In addition, we also cover the alternative delivery routes, such as intranasal and convection-enhanced diffusion methods, and disruption of the BBB for brain targeting.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date (Electronic): 11 December 2018
                Publication date Collection: December 2018
                Volume: 10
                Issue: 4
                Electronic Location Identifier: 269
                Affiliations
                [1 ]Emergency University Hospital, Bucharest, Romania, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; telepapa@ 123456hotmail.com (D.M.T.); raluca.teleanu@ 123456umfcd.ro (R.I.T.)
                [2 ]Faculty of Engineering in Foreign Languages, Politehnica University of Bucharest, 060042 București, Romania; cristina.chircov@ 123456yahoo.com
                [3 ]Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, 060042 București, Romania; grumezescu@ 123456yahoo.com
                [4 ]ICUB-Research Institute of University of Bucharest, University of Bucharest, 36-46 M. Kogalniceanu Blvd., 050107 Bucharest, Romania
                Author notes
                [* ]Correspondence: avolceanov@ 123456yahoo.co.uk or adrian.volceanov@ 123456upb.ro ; Tel.: +40-21-402-39-97
                Author information
                https://orcid.org/0000-0002-7668-861X
                Article
                Publisher ID: pharmaceutics-10-00269
                DOI: 10.3390/pharmaceutics10040269
                PMC ID: 6321434
                PubMed ID: 30544966
                SO-VID: 2093232c-558f-438a-bd23-142c1a18e96e
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 15 November 2018
                Date accepted : 07 December 2018
                Categories
                Subject: Review

                Keywords: brain,brain cancer,alzheimer’s disease,parkinson’s disease,nanoparticles,brain delivery,liposomes,dendrimers,micelles,carbon nanotubes
                Data availability:
                Keywords: brain, brain cancer, alzheimer’s disease, parkinson’s disease, nanoparticles, brain delivery, liposomes, dendrimers, micelles, carbon nanotubes

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