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Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives

Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed...

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Autores principales: Kouhi, Aida, Pachipulusu, Vyshnavi, Kapenstein, Talya, Hu, Peisheng, Epstein, Alan L., Khawli, Leslie A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235515/
https://www.ncbi.nlm.nih.gov/pubmed/34208575
http://dx.doi.org/10.3390/ijms22126442
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author Kouhi, Aida
Pachipulusu, Vyshnavi
Kapenstein, Talya
Hu, Peisheng
Epstein, Alan L.
Khawli, Leslie A.
author_facet Kouhi, Aida
Pachipulusu, Vyshnavi
Kapenstein, Talya
Hu, Peisheng
Epstein, Alan L.
Khawli, Leslie A.
author_sort Kouhi, Aida
collection PubMed
description Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent.
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spelling pubmed-82355152021-06-27 Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives Kouhi, Aida Pachipulusu, Vyshnavi Kapenstein, Talya Hu, Peisheng Epstein, Alan L. Khawli, Leslie A. Int J Mol Sci Review Due to their high specificity, monoclonal antibodies have been widely investigated for their application in drug delivery to the central nervous system (CNS) for the treatment of neurological diseases such as stroke, Alzheimer’s, and Parkinson’s disease. Research in the past few decades has revealed that one of the biggest challenges in the development of antibodies for drug delivery to the CNS is the presence of blood–brain barrier (BBB), which acts to restrict drug delivery and contributes to the limited uptake (0.1–0.2% of injected dose) of circulating antibodies into the brain. This article reviews the various methods currently used for antibody delivery to the CNS at the preclinical stage of development and the underlying mechanisms of BBB penetration. It also describes efforts to improve or modulate the physicochemical and biochemical properties of antibodies (e.g., charge, Fc receptor binding affinity, and target affinity), to adapt their pharmacokinetics (PK), and to influence their distribution and disposition into the brain. Finally, a distinction is made between approaches that seek to modify BBB permeability and those that use a physiological approach or antibody engineering to increase uptake in the CNS. Although there are currently inherent difficulties in developing safe and efficacious antibodies that will cross the BBB, the future prospects of brain-targeted delivery of antibody-based agents are believed to be excellent. MDPI 2021-06-16 /pmc/articles/PMC8235515/ /pubmed/34208575 http://dx.doi.org/10.3390/ijms22126442 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kouhi, Aida
Pachipulusu, Vyshnavi
Kapenstein, Talya
Hu, Peisheng
Epstein, Alan L.
Khawli, Leslie A.
Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title_full Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title_fullStr Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title_full_unstemmed Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title_short Brain Disposition of Antibody-Based Therapeutics: Dogma, Approaches and Perspectives
title_sort brain disposition of antibody-based therapeutics: dogma, approaches and perspectives
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235515/
https://www.ncbi.nlm.nih.gov/pubmed/34208575
http://dx.doi.org/10.3390/ijms22126442
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