Intranasal Drug Delivery to the Brain

Chapter
Part of the AAPS Advances in the Pharmaceutical Sciences Series book 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.

Keywords

Permeability Surfactant Osteoporosis Schizophrenia Oligomer 

Notes

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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Copyright information

© American Association of Pharmaceutical Scientists 2014

Authors and Affiliations

  1. 1.Pharmaceutical Sciences DivisionUniversity of Wisconsin—Madison School of PharmacyMadisonUSA
  2. 2.Center for Neuroscience & Neuroscience Training ProgramUniversity of Wisconsin—MadisonMadisonUSA
  3. 3.Cellular and Molecular Pathology Graduate Training ProgramUniversity of Wisconsin—MadisonMadisonUSA
  4. 4.Clinical Neuroengineering Training ProgramUniversity of Wisconsin—MadisonMadisonUSA

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