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Pharmaceutics 2018, 10(3), 107; https://doi.org/10.3390/pharmaceutics10030107

Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery?

1
Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany
2
Faculty for Natural Sciences, University of Ulm, 89081 Ulm, Germany
3
Faculty of Medicine, Graduate School ‘Molecular Medicine’, University of Ulm, 89081 Ulm, Germany
4
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Philipps-University Marburg, 35032 Marburg, Germany
5
Chair of Zoology, Technical University of Munich, 85354 Freising-Weihenstephan, Germany
*
Author to whom correspondence should be addressed.
Received: 24 June 2018 / Revised: 19 July 2018 / Accepted: 20 July 2018 / Published: 26 July 2018
(This article belongs to the Special Issue Nose to Brain Delivery)
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Abstract

Background: The use of therapeutic antibodies for the treatment of neurological diseases is of increasing interest. Nose-to-brain drug delivery is one strategy to bypass the blood brain barrier. The neonatal Fc receptor (FcRn) plays an important role in transepithelial transcytosis of immunoglobulin G (IgG). Recently, the presence of the FcRn was observed in nasal respiratory mucosa. The aim of the present study was to determine the presence of functional FcRn in olfactory mucosa and to evaluate its role in drug delivery. Methods: Immunoreactivity and messenger RNA (mRNA) expression of FcRn was determined in ex vivo porcine olfactory mucosa. Uptake of IgG was performed in a side-by-side cell and analysed by immunofluorescence. Results: FcRn was found in epithelial and basal cells of the olfactory epithelium as well as in glands, cavernous bodies and blood vessels. Allogenic porcine IgGs were found time-dependently in the lamina propria and along axonal bundles, while only small amounts of xenogenic human IgGs were detected. Interestingly, lymphoid follicles were spared from allogenic IgGs. Conclusion: Fc-mediated transport of IgG across the nasal epithelial barrier may have significant potential for intranasal delivery, but the relevance of immune interaction in lymphoid follicles must be clarified to avoid immunogenicity. View Full-Text
Keywords: olfactory epithelium; respiratory epithelium; nasal mucosa; NALT; lymphoid follicles; neuronal bundles; antibody; permeation; nose to brain; drug delivery olfactory epithelium; respiratory epithelium; nasal mucosa; NALT; lymphoid follicles; neuronal bundles; antibody; permeation; nose to brain; drug delivery
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Ladel, S.; Flamm, J.; Zadeh, A.S.; Filzwieser, D.; Walter, J.-C.; Schlossbauer, P.; Kinscherf, R.; Lischka, K.; Luksch, H.; Schindowski, K. Allogenic Fc Domain-Facilitated Uptake of IgG in Nasal Lamina Propria: Friend or Foe for Intranasal CNS Delivery? Pharmaceutics 2018, 10, 107.

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