Direct nose to brain drug delivery via integrated nerve pathways bypassing the blood-brain barrier: an excellent platform for brain targeting

Expert Opin Drug Deliv. 2013 Jul;10(7):957-72. doi: 10.1517/17425247.2013.790887. Epub 2013 Apr 16.


Introduction: The blood-brain barrier (BBB) represents a stringent barrier for delivery of neurotherapeutics in vivo. An attempt to overcome this barrier is represented by the direct transport of drugs from the nose to the brain along the olfactory and trigeminal nerve pathways. These nerve pathways initiate in the nasal cavity at olfactory neuroepithelium and terminate in the brain. An enormous range of neurotherapeutics, both macromolecules and low molecular weight drugs, can be delivered to the central nervous system (CNS) via this route.

Areas covered: Present review highlights the literature on the anatomy-physiology of the nasal cavity, pathways and mechanisms of neurotherapeutic transport across nasal epithelium and their biofate and various strategies to enhance direct nose to brain drug delivery. The authors also emphasize a variety of drug molecules and carrier systems delivered via this route for treating CNS disorders. Patents related to direct nose to brain drug delivery systems have also been listed.

Expert opinion: Direct nose to brain drug delivery system is a practical, safe, non-invasive and convenient form of formulation strategy and could be viewed as an excellent alternative approach to conventional dosage forms. Existence of a direct transport route from the nasal cavity to the brain, bypassing the BBB, would offer an exciting mode of delivering neurotherapeutic agents.

Publication types

  • Review

MeSH terms

  • Administration, Intranasal
  • Biological Transport
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism*
  • Drug Delivery Systems*
  • Humans
  • Nasal Mucosa / innervation
  • Olfactory Pathways / metabolism*
  • Pharmaceutical Preparations / administration & dosage*
  • Trigeminal Nerve / metabolism*


  • Pharmaceutical Preparations