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Tailoring Formulations for Intranasal Nose-to-Brain Delivery: A Review on Architecture, Physico-Chemical Characteristics and Mucociliary Clearance of the Nasal Olfactory Mucosa

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Gänger, Stella, Schindowski, Katharina·2018·Pharmaceutics
DOI 10.3390/pharmaceutics10030116PMC PMC6161189
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Abstract

The blood-brain barrier and the blood-cerebrospinal fluid barrier are major obstacles in central nervous system (CNS) drug delivery, since they block most molecules from entering the brain. Alternative drug delivery routes like intraparenchymal or intrathecal are invasive methods with a remaining risk of infections. In contrast, nose-to-brain delivery is a minimally invasive drug administration pathway, which bypasses the blood-brain barrier as the drug is directed from the nasal cavity to the brain. In particular, the skull base located at the roof of the nasal cavity is in close vicinity to the CNS. This area is covered with olfactory mucosa. To design and tailor suitable formulations for nose-to-brain drug delivery, the architecture, structure and physico-chemical characteristics of the mucosa are important criteria. Hence, here we review the state-of-the-art knowledge about the characteristics of the nasal and, in particular, the olfactory mucosa needed for a rational design of intranasal formulations and dosage forms. Also, the information is suitable for the development of systemic or local intranasal drug delivery as well as for intranasal vaccinations.

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  • The olfactory nerve-olfactory bulb-brain route is the shortest and most direct nose-to-brain route, allowing delivery within 1.5-6 h, and via olfactory epithelial cells in only a few minutes.

    “Specifically, (1) is the shortest and most direct route. It has been used advantageously to deliver drugs at high speed. It was possible to complete the delivery within the time window of 1.5-6 h, and even the route via olfactory epithelial cells takes only a few minutes.161”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [161]

    Section 5.1 (page not available) reports 1.5–6 hours for transport via the olfactory nerve and describes the olfactory pathway as more feasible than the longer trigeminal route. It also reports nose-to-brain delivery within minutes, but does not assign that speed to transport via olfactory epithelial cells; instead, it describes intracellular neuronal transport as slow and unlikely to be the primary route for rapid delivery. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Gänger, S., & Schindowski, K.
Affiliations
  • Universität Ulm (DE)
  • University of Applied Sciences Biberach (DE)
Corresponding author
Schindowski, Katharina
ORCID
Schindowski, Katharina
Venue
Pharmaceutics
Publisher
MDPI AG
Published
2018-08-03
Volume
10
Issue
3
Pages
116
ISSN
1999-4923 (ISSN-L)
DOI
10.3390/pharmaceutics10030116
PMC
PMC6161189
OpenAlex
W2887204204
Cited by
447
References
9
Citations by year
2026: 54 · 2025: 72 · 2024: 64 · 2023: 67 · 2022: 58 · 2021: 71 · 2020: 45 · 2019: 15 · 2018: 1
FWCI
2.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Pharmaceutics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) (submittedVersion, cc-by)
  • Universität Ulm, Kommunikations- und Informationszentrum (kiz) (cc-by)
Funders
Horizon 2020 Framework Programme (721098)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
  • Health Sciences › Medicine › Surgery › Head and Neck Surgical Oncology
Keywords
nose-to-brain delivery, intranasal drug delivery, olfactory epithelium, mucociliary clearance, blood-brain barrier, blood-CSF barrier, brain drug delivery, intranasal formulation, pharmaceutical dosage forms, intranasal immunization, skull base

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