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Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) trea...

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Autores principales: Moscariello, Pierpaolo, Ng, David Y. W., Jansen, Malin, Weil, Tanja, Luhmann, Heiko J., Hedrich, Jana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979778/
https://www.ncbi.nlm.nih.gov/pubmed/29876217
http://dx.doi.org/10.1002/advs.201700897
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author Moscariello, Pierpaolo
Ng, David Y. W.
Jansen, Malin
Weil, Tanja
Luhmann, Heiko J.
Hedrich, Jana
author_facet Moscariello, Pierpaolo
Ng, David Y. W.
Jansen, Malin
Weil, Tanja
Luhmann, Heiko J.
Hedrich, Jana
author_sort Moscariello, Pierpaolo
collection PubMed
description Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here.
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spelling pubmed-59797782018-06-06 Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates Moscariello, Pierpaolo Ng, David Y. W. Jansen, Malin Weil, Tanja Luhmann, Heiko J. Hedrich, Jana Adv Sci (Weinh) Full Papers Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here. John Wiley and Sons Inc. 2018-02-23 /pmc/articles/PMC5979778/ /pubmed/29876217 http://dx.doi.org/10.1002/advs.201700897 Text en © 2018 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim 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.
spellingShingle Full Papers
Moscariello, Pierpaolo
Ng, David Y. W.
Jansen, Malin
Weil, Tanja
Luhmann, Heiko J.
Hedrich, Jana
Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title_full Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title_fullStr Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title_full_unstemmed Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title_short Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates
title_sort brain delivery of multifunctional dendrimer protein bioconjugates
topic Full Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979778/
https://www.ncbi.nlm.nih.gov/pubmed/29876217
http://dx.doi.org/10.1002/advs.201700897
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