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Updated: Oct 12, 2025

Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols
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Modeling and Simulations of Olfactory Drug Delivery with Passive and Active Controls of Nasally Inhaled Pharmaceutical Aerosols

Published on: May 20, 2016

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

Frank Maigler1,2, Simone Ladel1,2, Johannes Flamm1,2

  • 1Institute of Applied Biotechnology, University of Applied Science Biberach, Hubertus-Liebrecht Straße 35, 88400 Biberach, Germany.

Pharmaceutics
|November 27, 2021
PubMed

Insights

A refined intranasal drug delivery technique precisely targets the mouse olfactory region for enhanced central nervous system (CNS) delivery, improving brain targeting and reducing peripheral effects.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Drug Delivery Systems

Background:

  • Intranasal drug delivery offers a non-invasive route to the CNS.
  • Current methods lack precision and standardization, limiting study quality.
  • Region-specific application techniques in mice are needed.

Purpose of the Study:

  • To validate a refined catheter-based intranasal technique against conventional methods.
  • To achieve region-specific drug delivery to the olfactory or respiratory nasal regions.
  • To evaluate brain targeting and peripheral distribution of administered substances.

Main Methods:

  • Validation of a catheter-based intranasal technique versus pipette-based delivery.
  • Region-specific administration targeting the olfactory mucosa in mice.
  • Quantification of fluorescein, insulin detemir, and monoclonal antibodies (mAbs) distribution.

Main Results:

  • Olfactory region administration achieved >20% fluorescein dose in olfactory bulbs.
  • No peripheral bioactivity observed for insulin detemir.
  • Fc-dependent uptake of IgG1 mAbs (11C7, P3X) to cortex and hippocampus via olfactory pathway.
  • Minimal CNS uptake of scFv 11C7.
  • Elimination of IgG1 was antigen-dependent.

Conclusions:

  • Region-specific intranasal administration via the olfactory region enhances brain targeting.
  • This method reduces peripheral drug exposure and targeting.
  • The validated technique shows significant clinical potential for CNS drug delivery.
Keywords:
CNS drug deliveryCNS targetingbiopharmaceuticalsnose to brain drug deliveryrefined drug deliverytherapeutic antibodies

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