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

Pharmaceutics

Harald Luksch¹  Katharina Lischka¹  Ralf Kinscherf²  Simone Ladel³  Patrick Schlossbauer³  Johannes Flamm³  ArghavanSoleimani Zadeh³  Julia-Christina Walter³  Katharina Schindowski³  Dorothea Filzwieser³ 

[1] Chair of Zoology, Technical University of Munich, 85354 Freising-Weihenstephan, Germany;Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Philipps-University Marburg, 35032 Marburg, Germany;Institute of Applied Biotechnology, University of Applied Science Biberach, 88400 Biberach, Germany;

关键词: olfactory epithelium;    respiratory epithelium;    nasal mucosa;    NALT;    lymphoid follicles;    neuronal bundles;    antibody;    permeation;    nose to brain;    drug delivery;   

DOI  :  10.3390/pharmaceutics10030107

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown