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Intranasal Drug Delivery to the Brain

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Drug Delivery to the Brain

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 10))

Abstract

Drug delivery into the central nervous system (CNS) compartment is often restricted by the blood–brain barrier (BBB) and blood–cerebrospinal fluid barriers (BCSFB) that separate the blood from brain interstitial and cerebrospinal fluids, respectively. New strategies to circumvent the BBB are greatly needed to utilize polar pharmaceuticals and large biotherapeutics for CNS disease treatment because the BBB is typically impermeable to such compounds. Intranasal administration is a noninvasive method of drug delivery that potentially allows even large biotherapeutics access to the CNS along extracellular pathways associated with the olfactory and trigeminal nerves. Rapid effects, ease of self-administration, and the potential for frequent, chronic dosing are among the potential advantages of the intranasal route. This chapter provides an overview of the unique anatomic and physiologic attributes of the nasal mucosa and its associated cranial nerves that allow small but significant fractions of certain intranasally applied drugs to transfer across the nasal epithelia and subsequently be transported directly into the CNS. We also review the preclinical and clinical literature related to intranasal targeting of biotherapeutics to the CNS and speculate on future directions.

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Acknowledgements

Portions of this work were supported by the University of Wisconsin-Madison School of Pharmacy, the Graduate School at the University of Wisconsin, the Michael J. Fox Foundation for Parkinson’s Research, the Wisconsin Alzheimer’s Disease Research Center (NIH P50-AG033514), and the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS; grant UL1TR000427). All content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Robert Thorne acknowledges periodically receiving honoraria for speaking to organizations within academia, foundations, and the biotechnology and pharmaceutical industry as well as occasional service as a consultant on CNS drug delivery to industry. Jeffrey Lochhead and Robert Thorne also acknowledge being inventors on patents and/or patent applications related to intranasal drug delivery.

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Authors and Affiliations

  1. Pharmaceutical Sciences Division, University of Wisconsin—Madison School of Pharmacy, Madison, WI, USA

    Jeffrey J. Lochhead & Robert G. Thorne

  2. Center for Neuroscience & Neuroscience Training Program, University of Wisconsin—Madison, Madison, WI, USA

    Robert G. Thorne

  3. Cellular and Molecular Pathology Graduate Training Program, University of Wisconsin—Madison, Madison, WI, USA

    Robert G. Thorne

  4. Clinical Neuroengineering Training Program, University of Wisconsin—Madison, Madison, WI, USA

    Robert G. Thorne

Authors
  1. Jeffrey J. Lochhead
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  2. Robert G. Thorne
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Correspondence to Robert G. Thorne .

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Editors and Affiliations

  1. Pharmaceutical Biosciences, Uppsala University Pharmacokinetics and Drug Therapy, Uppsala, Sweden

    Margareta Hammarlund-Udenaes

  2. LACDR/Pharmacology, Leiden University, Leiden, The Netherlands

    Elizabeth C.M. de Lange

  3. Pharmaceutical Sciences Division, University of Wisconsin-Madison School of Pharmacy, Madison, Wisconsin, USA

    Robert G. Thorne

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© 2014 American Association of Pharmaceutical Scientists

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Lochhead, J.J., Thorne, R.G. (2014). Intranasal Drug Delivery to the Brain. In: Hammarlund-Udenaes, M., de Lange, E., Thorne, R. (eds) Drug Delivery to the Brain. AAPS Advances in the Pharmaceutical Sciences Series, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9105-7_14

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