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ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier

Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery sys...

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Autores principales: Topal, Gizem Rüya, Mészáros, Mária, Porkoláb, Gergő, Szecskó, Anikó, Polgár, Tamás Ferenc, Siklós, László, Deli, Mária A., Veszelka, Szilvia, Bozkir, Asuman
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824445/
https://www.ncbi.nlm.nih.gov/pubmed/33383743
http://dx.doi.org/10.3390/pharmaceutics13010038
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author Topal, Gizem Rüya
Mészáros, Mária
Porkoláb, Gergő
Szecskó, Anikó
Polgár, Tamás Ferenc
Siklós, László
Deli, Mária A.
Veszelka, Szilvia
Bozkir, Asuman
author_facet Topal, Gizem Rüya
Mészáros, Mária
Porkoláb, Gergő
Szecskó, Anikó
Polgár, Tamás Ferenc
Siklós, László
Deli, Mária A.
Veszelka, Szilvia
Bozkir, Asuman
author_sort Topal, Gizem Rüya
collection PubMed
description Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles.
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spelling pubmed-78244452021-01-24 ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier Topal, Gizem Rüya Mészáros, Mária Porkoláb, Gergő Szecskó, Anikó Polgár, Tamás Ferenc Siklós, László Deli, Mária A. Veszelka, Szilvia Bozkir, Asuman Pharmaceutics Article Pharmacological treatment of central nervous system (CNS) disorders is difficult, because the blood–brain barrier (BBB) restricts the penetration of many drugs into the brain. To solve this unmet therapeutic need, nanosized drug carriers are the focus of research efforts to develop drug delivery systems for the CNS. For the successful delivery of nanoparticles (NPs) to the brain, targeting ligands on their surface is necessary. Our research aim was to design a nanoscale drug delivery system for a more efficient transfer of donepezil, an anticholinergic drug in the therapy of Alzheimer’s disease across the BBB. Rhodamine B-labeled solid lipid nanoparticles with donepezil cargo were prepared and targeted with apolipoprotein E (ApoE), a ligand of BBB receptors. Nanoparticles were characterized by measurement of size, polydispersity index, zeta potential, thermal analysis, Fourier-transform infrared spectroscopy, in vitro release, and stability. Cytotoxicity of nanoparticles were investigated by metabolic assay and impedance-based cell analysis. ApoE-targeting increased the uptake of lipid nanoparticles in cultured brain endothelial cells and neurons. Furthermore, the permeability of ApoE-targeted nanoparticles across a co-culture model of the BBB was also elevated. Our data indicate that ApoE, which binds BBB receptors, can potentially be exploited for successful CNS targeting of solid lipid nanoparticles. MDPI 2020-12-29 /pmc/articles/PMC7824445/ /pubmed/33383743 http://dx.doi.org/10.3390/pharmaceutics13010038 Text en © 2020 by the authors. 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/).
spellingShingle Article
Topal, Gizem Rüya
Mészáros, Mária
Porkoláb, Gergő
Szecskó, Anikó
Polgár, Tamás Ferenc
Siklós, László
Deli, Mária A.
Veszelka, Szilvia
Bozkir, Asuman
ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title_full ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title_fullStr ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title_full_unstemmed ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title_short ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood–Brain Barrier
title_sort apoe-targeting increases the transfer of solid lipid nanoparticles with donepezil cargo across a culture model of the blood–brain barrier
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824445/
https://www.ncbi.nlm.nih.gov/pubmed/33383743
http://dx.doi.org/10.3390/pharmaceutics13010038
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