Selective CNS Targeting and Distribution with a Refined Region-Specific Intranasal Delivery Technique via the Olfactory Mucosa
| Autor: | Claudia Pitzer, Sebastian Spiegel, Johannes Flamm, Frank Maigler, Sunniva Hartung, Ronja Völk, Carmen Hamp, Katharina Schindowski, Katharina Eberle, Arghavan Soleimanizadeh, Stefanie Kiderlen, Barbara Kurpiers, Lukas Krainer, Simone Ladel, Stella Gänger, Rebecca Hermann |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Olfactory system
CNS drug delivery Pharmaceutical Science Hippocampus therapeutic antibodies Pharmacology Article refined drug delivery 03 medical and health sciences chemistry.chemical_compound Olfactory mucosa CNS targeting 0302 clinical medicine nose to brain drug delivery Pharmacy and materia medica Antigen Medicine Distribution (pharmacology) Fluorescein Olfactory Region 030304 developmental biology 0303 health sciences business.industry biopharmaceuticals RS1-441 medicine.anatomical_structure chemistry Nasal administration business 030217 neurology & neurosurgery |
| Zdroj: | Pharmaceutics, Vol 13, Iss 1904, p 1904 (2021) Pharmaceutics Volume 13 Issue 11 |
| ISSN: | 1999-4923 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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