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Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins

Nose-to-brain delivery presents a promising alternative route compared to classical blood–brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to...

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Autores principales: Gabold, Bettina, Adams, Friederike, Brameyer, Sophie, Jung, Kirsten, Ried, Christian L., Merdan, Thomas, Merkel, Olivia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892103/
https://www.ncbi.nlm.nih.gov/pubmed/36207657
http://dx.doi.org/10.1007/s13346-022-01245-z
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author Gabold, Bettina
Adams, Friederike
Brameyer, Sophie
Jung, Kirsten
Ried, Christian L.
Merdan, Thomas
Merkel, Olivia M.
author_facet Gabold, Bettina
Adams, Friederike
Brameyer, Sophie
Jung, Kirsten
Ried, Christian L.
Merdan, Thomas
Merkel, Olivia M.
author_sort Gabold, Bettina
collection PubMed
description Nose-to-brain delivery presents a promising alternative route compared to classical blood–brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide–alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110–150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air–liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-022-01245-z.
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spelling pubmed-98921032023-02-03 Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins Gabold, Bettina Adams, Friederike Brameyer, Sophie Jung, Kirsten Ried, Christian L. Merdan, Thomas Merkel, Olivia M. Drug Deliv Transl Res Original Article Nose-to-brain delivery presents a promising alternative route compared to classical blood–brain barrier passage, especially for the delivery of high molecular weight drugs. In general, macromolecules are rapidly degraded in physiological environment. Therefore, nanoparticulate systems can be used to protect biomolecules from premature degradation. Furthermore, targeting ligands on the surface of nanoparticles are able to improve bioavailability by enhancing cellular uptake due to specific binding and longer residence time. In this work, transferrin-decorated chitosan nanoparticles are used to evaluate the passage of a model protein through the nasal epithelial barrier in vitro. It was demonstrated that strain-promoted azide–alkyne cycloaddition reaction can be utilized to attach a functional group to both transferrin and chitosan enabling a rapid covalent surface-conjugation under mild reaction conditions after chitosan nanoparticle preparation. The intactness of transferrin and its binding efficiency were confirmed via SDS-PAGE and SPR measurements. Resulting transferrin-decorated nanoparticles exhibited a size of about 110–150 nm with a positive surface potential. Nanoparticles with the highest amount of surface bound targeting ligand also displayed the highest cellular uptake into a human nasal epithelial cell line (RPMI 2650). In an air–liquid interface co-culture model with glioblastoma cells (U87), transferrin-decorated nanoparticles showed a faster passage through the epithelial cell layer as well as increased cellular uptake into glioblastoma cells. These findings demonstrate the beneficial characteristics of a specific targeting ligand. With this chemical and technological formulation concept, a variety of targeting ligands can be attached to the surface after nanoparticle formation while maintaining cargo integrity. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13346-022-01245-z. Springer US 2022-10-07 2023 /pmc/articles/PMC9892103/ /pubmed/36207657 http://dx.doi.org/10.1007/s13346-022-01245-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Gabold, Bettina
Adams, Friederike
Brameyer, Sophie
Jung, Kirsten
Ried, Christian L.
Merdan, Thomas
Merkel, Olivia M.
Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title_full Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title_fullStr Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title_full_unstemmed Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title_short Transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
title_sort transferrin-modified chitosan nanoparticles for targeted nose-to-brain delivery of proteins
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892103/
https://www.ncbi.nlm.nih.gov/pubmed/36207657
http://dx.doi.org/10.1007/s13346-022-01245-z
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