Impact of Glycosylation and Species Origin on the Uptake and Permeation of IgGs through the Nasal Airway Mucosa.
IgG permeation
RPMI 2650
barrier model
blood-brain barrier
drug delivery
nose-to-brain
olfactory epithelium
primary cells
respiratory epithelium
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
23 Oct 2020
23 Oct 2020
Historique:
received:
26
09
2020
revised:
18
10
2020
accepted:
21
10
2020
entrez:
29
10
2020
pubmed:
30
10
2020
medline:
30
10
2020
Statut:
epublish
Résumé
Although we have recently reported the involvement of neonatal Fc receptor (FcRn) in intranasal transport, the transport mechanisms are far from being elucidated. Ex vivo porcine olfactory tissue, primary cells from porcine olfactory epithelium (OEPC) and the human cell line RPMI 2650 were used to evaluate the permeation of porcine and human IgG antibodies through the nasal mucosa. IgGs were used in their wild type and deglycosylated form to investigate the impact of glycosylation. Further, the expression of FcRn and Fc-gamma receptor (FCGR) and their interaction with IgG were analyzed. Comparable permeation rates for human and porcine IgG were observed in OEPC, which display the highest expression of FcRn. Only traces of porcine IgGs could be recovered at the basolateral compartment in ex vivo olfactory tissue, while human IgGs reached far higher levels. Deglycosylated human IgG showed significantly higher permeation in comparison to the wild type in RPMI 2650 and OEPC, but insignificantly elevated in the ex vivo model. An immunoprecipitation with porcine primary cells and tissue identified FCGR2 as a potential interaction partner in the nasal mucosa. Glycosylation sensitive receptors appear to be involved in the uptake, transport, but also degradation of therapeutic IgGs in the airway epithelial layer.
Identifiants
pubmed: 33114132
pii: pharmaceutics12111014
doi: 10.3390/pharmaceutics12111014
pmc: PMC7690786
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : H2020 Industrial Leadership
ID : 721098
Organisme : Bundesministerium für Wirtschaft und Energie
ID : ALIVE
Organisme : Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
ID : FcRn in Drug Delivery
Organisme : Stiftung der Deutschen Wirtschaft
ID : Klaus Murmann fellowship to SL and JF
Déclaration de conflit d'intérêts
The authors declare no conflict of interest.
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