Tissue-based in vitro and ex vivo models for nasal permeability studies

Natalia Porfiryeva, Alejandro Sosnik

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review


The nasal epithelium is a complex, highly vascularized, and innervated cellular structure that owing to a very high surface area has been extensively investigated not only for local drug delivery (topical administration) but also for systemic one (transnasal route). More recently, the evidence that there is a direct pathway from the nasal mucosa to the central nervous system that surpasses the blood–brain barrier, known as the nose-to-brain pathway, has attracted the attention of researchers and clinicians as a strategy to target different kinds of therapeutic agents to the brain in the so-called intranasal route. Advantages of this administration route also include simplicity and minimal invasiveness, and it is appropriate for older adults and children. Intranasal administration has been attempted with different types of formulations, from aqueous and nonsaqueous solutions to drug-loaded colloidal systems, being mucoadhesive and mucus-penetrating polymeric nanoparticles with a diameter of up to 300nm among clinically promising. At the same time, there exists controversy about the transport mechanisms involved and the contribution of each one to the nose-to-brain delivery. The complex structure of the nose and the presence of mucociliary clearance have challenged our ability to find reliable in vivo models to assess the performance of formulations for intranasal delivery because the available animal models (e.g., rodents) do not accurately mimic the human nasal mucosa. In addition, the use of animal models at early development stages is ethically questionable. In this framework, the finding of reliable and robust in vitro and ex vivo models would be crucial to systematically evaluate the nasal permeability of different types of formulations as a preamble to preclinical studies. The present chapter will briefly overview the most relevant structural features of the nasal mucosa and then, discuss the different models proposed.

Original languageEnglish
Title of host publicationConcepts and Models for Drug Permeability Studies
Subtitle of host publicationCell and Tissue based In Vitro Culture Models
Number of pages25
ISBN (Electronic)9780443155109
StatePublished - 1 Jan 2024


  • Excised nasal mucosa models
  • Intranasal route
  • Localized drug delivery
  • Nasal mucosa
  • Nose-to-brain pathway
  • Systemic drug delivery
  • Targeting to the central nervous system
  • Transnasal route

ASJC Scopus subject areas

  • General Medicine
  • General Pharmacology, Toxicology and Pharmaceutics


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