Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa.
CNS drug delivery
CNS targeting
biopharmaceuticals
nose to brain drug delivery
refined drug delivery
therapeutic antibodies
Journal
Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003
Informations de publication
Date de publication:
10 Nov 2021
10 Nov 2021
Historique:
received:
01
10
2021
revised:
04
11
2021
accepted:
05
11
2021
entrez:
27
11
2021
pubmed:
28
11
2021
medline:
28
11
2021
Statut:
epublish
Résumé
Intranasal drug delivery is a promising approach for the delivery of drugs to the CNS, but too heterogenous, unprecise delivery methods without standardization decrease the quality of many studies in rodents. Thus, the lack of a precise and region-specific application technique for mice is a major drawback. In this study, a previously developed catheter-based refined technique was validated against the conventional pipette-based method and used to specifically reach the olfactory or the respiratory nasal regions. This study successfully demonstrated region-specific administration at the olfactory mucosa resulting in over 20% of the administered fluorescein dose in the olfactory bulbs, and no peripheral bioactivity of insulin detemir and Fc-dependent uptake of two murine IgG1 (11C7 and P3X) along the olfactory pathway to cortex and hippocampus. An scFv of 11C7 showed hardly any uptake to the CNS. Elimination was dependent on the presence of the IgG's antigen. In summary, it was successfully demonstrated that region-specific intranasal administration via the olfactory region resulted in improved brain targeting and reduced peripheral targeting in mice. The data are discussed with regard to their clinical potential.
Identifiants
pubmed: 34834319
pii: pharmaceutics13111904
doi: 10.3390/pharmaceutics13111904
pmc: PMC8620656
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : European Commission
ID : N2B-patch' Grant No. 721098
Organisme : Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
ID : FcRn in N2B
Organisme : Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg
ID : funds and fellowship by the Ulm and Biberach joint graduate school in pharmaceutical biotechnology
Organisme : Federal Institute for Risk Assessment
ID : ZEBET '3D für 3R'
Organisme : Federal Ministry for Economic Affairs and Energy
ID : ALIVE
Organisme : Stiftung der Deutschen Wirtschaft
ID : fellowships (S.L. and J.F.)
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