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Can Nasal Drug Delivery Bypass the Blood-Brain Barrier?

Questioning the Direct Transport Theory

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Abstract

The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS. In the analysis the large anatomical differences between the olfactory areas of animals and humans and the experimental conditions used were evaluated. The aim of this paper was to establish the actual evidence for the feasibility of this direct transport route in humans.

Twelve papers presented a sound experimental design to study direct nose to CNS transport of drugs based on the authors’ criteria. Of these, only two studies in rats were able to provide results that can be seen as an indication for direct transport from the nose to the CNS. No pharmacokinetic evidence could be found to support a claim that nasal administration of drugs in humans will result in an enhanced delivery to their target sites in the brain compared with intravenous administration of the same drug under similar dosage conditions.

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Notes

  1. The total number of claims (n =17)exceeds the number of papers (n =12)as some papers tested more than one compound.

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The authors used no sources of funding in the writing of this article. The authors have no conflicts of interest that are directly relevant to the content of this article.

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  1. Leiden/Amsterdam Centre for Drug Research, Leiden University, P.O. Box 9502, Leiden, 2300 RA, The Netherlands

    Frans W. H. M. Merkus

  2. Pfizer Global Research and Development, Sandwich, UK

    Mascha P. van den Berg

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  1. Frans W. H. M. Merkus
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  2. Mascha P. van den Berg
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Correspondence to Frans W. H. M. Merkus.

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Merkus, F.W.H.M., van den Berg, M.P. Can Nasal Drug Delivery Bypass the Blood-Brain Barrier?. Drugs R D 8, 133–144 (2007). https://doi.org/10.2165/00126839-200708030-00001

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