Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa

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 d...

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Autores principales:	Frank Maigler, Simone Ladel, Johannes Flamm, Stella Gänger, Barbara Kurpiers, Stefanie Kiderlen, Ronja Völk, Carmen Hamp, Sunniva Hartung, Sebastian Spiegel, Arghavan Soleimanizadeh, Katharina Eberle, Rebecca Hermann, Lukas Krainer, Claudia Pitzer, Katharina Schindowski
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	CNS drug delivery nose to brain drug delivery biopharmaceuticals therapeutic antibodies CNS targeting refined drug delivery Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/9cc3636f978846548c41bf6687931047
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spelling	oai:doaj.org-article:9cc3636f978846548c41bf66879310472021-11-25T18:41:40ZSelective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa10.3390/pharmaceutics131119041999-4923https://doaj.org/article/9cc3636f978846548c41bf66879310472021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1904https://doaj.org/toc/1999-4923Intranasal 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.Frank MaiglerSimone LadelJohannes FlammStella GängerBarbara KurpiersStefanie KiderlenRonja VölkCarmen HampSunniva HartungSebastian SpiegelArghavan SoleimanizadehKatharina EberleRebecca HermannLukas KrainerClaudia PitzerKatharina SchindowskiMDPI AGarticleCNS drug deliverynose to brain drug deliverybiopharmaceuticalstherapeutic antibodiesCNS targetingrefined drug deliveryPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1904, p 1904 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CNS drug delivery nose to brain drug delivery biopharmaceuticals therapeutic antibodies CNS targeting refined drug delivery Pharmacy and materia medica RS1-441
spellingShingle	CNS drug delivery nose to brain drug delivery biopharmaceuticals therapeutic antibodies CNS targeting refined drug delivery Pharmacy and materia medica RS1-441 Frank Maigler Simone Ladel Johannes Flamm Stella Gänger Barbara Kurpiers Stefanie Kiderlen Ronja Völk Carmen Hamp Sunniva Hartung Sebastian Spiegel Arghavan Soleimanizadeh Katharina Eberle Rebecca Hermann Lukas Krainer Claudia Pitzer Katharina Schindowski Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
description	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.
format	article
author	Frank Maigler Simone Ladel Johannes Flamm Stella Gänger Barbara Kurpiers Stefanie Kiderlen Ronja Völk Carmen Hamp Sunniva Hartung Sebastian Spiegel Arghavan Soleimanizadeh Katharina Eberle Rebecca Hermann Lukas Krainer Claudia Pitzer Katharina Schindowski
author_facet	Frank Maigler Simone Ladel Johannes Flamm Stella Gänger Barbara Kurpiers Stefanie Kiderlen Ronja Völk Carmen Hamp Sunniva Hartung Sebastian Spiegel Arghavan Soleimanizadeh Katharina Eberle Rebecca Hermann Lukas Krainer Claudia Pitzer Katharina Schindowski
author_sort	Frank Maigler
title	Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
title_short	Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
title_full	Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
title_fullStr	Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
title_full_unstemmed	Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
title_sort	selective cns targeting and distribution with a refined region-specific intranasal delivery technique via the olfactory mucosa
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9cc3636f978846548c41bf6687931047
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Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa

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