Intranasal Nose-to-Brain Drug Delivery via the Olfactory Region in Mice: Two In-Depth Protocols for Region-Specific Intranasal Application of Antibodies and for Expression Analysis of Fc Receptors via In Situ Hybridization in the Nasal Mucosa

Methods Mol Biol. 2024:2754:387-410. doi: 10.1007/978-1-0716-3629-9_21.

Abstract

A region-specific catheter-based intranasal administration method was successfully developed, established, and validated as reported previously. By using this method, drugs can be applicated specifically to the olfactory region. Thereby, intranasally administered drugs could be delivered via neuronal connections to the central nervous system. Here, we present a detailed protocol with a step-by-step procedure for nose-to-brain delivery via the olfactory mucosa.Fc receptors such as the neonatal Fc receptor (FcRn) and potentially Fcγ receptor IIb (FcγRIIb) are involved in the uptake and transport of antibodies via the olfactory nasal mucosa. To better characterize their expression levels and their role in CNS drug delivery via the nose, an in situ hybridization (ISH) protocol was adapted for nasal mucosa samples and described in abundant details.

Keywords: CNS delivery; In situ hybridization; Intranasal delivery; Nose-to-brain drug delivery; Olfactory mucosa.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Antibodies / metabolism
  • Brain* / metabolism
  • Drug Delivery Systems / methods
  • In Situ Hybridization
  • Mice
  • Nasal Mucosa*
  • Pharmaceutical Preparations / metabolism
  • Receptors, Fc / genetics
  • Receptors, Fc / metabolism

Substances

  • Pharmaceutical Preparations
  • Antibodies
  • Receptors, Fc