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.
Highlights
Biopharmaceuticals are of increasing importance in the therapy of various diseases
As the feasibility of nose to brain (N2B) drug delivery was already shown for sumatriptan, oxytocin, insulin, and some other drugs, it is of particular interest to investigate whether the N2B route is suitable for proteins with a higher molecular weight such as antibodies [7,12,13,14]
The regio olfactoria is the region of interest with regard to N2B drug delivery, as the epithelium is widely spanned with olfactory sensory neurons that are projecting into the brain, but it is innervated by the trigeminal branches that connect to the brain stem [33]
Summary
Since the development of the hybridoma technology by Köhler and Milstein, some of the most important biopharmaceutical molecules are antibodies, in particular immunoglobulin G (IgGs) [1,2]. Despite their great therapeutic potential, the tissue penetration of large molecules like IgGs is a critical aspect for the development of therapies and administration routes, in particular for neurological disorders. One strategy to bypass the BBB is to deliver drugs to the CNS by intranasal drug delivery. 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. 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
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