Intranasal delivery of biologics to the central nervous system

Adv Drug Deliv Rev. 2012 May 15;64(7):614-28. doi: 10.1016/j.addr.2011.11.002. Epub 2011 Nov 15.


Treatment of central nervous system (CNS) diseases is very difficult due to the blood-brain barrier's (BBB) ability to severely restrict entry of all but small, non-polar compounds. Intranasal administration is a non-invasive method of drug delivery which may bypass the BBB to allow therapeutic substances direct access to the CNS. Intranasal delivery of large molecular weight biologics such as proteins, gene vectors, and stem cells is a potentially useful strategy to treat a variety of diseases/disorders of the CNS including stroke, Parkinson's disease, multiple sclerosis, Alzheimer's disease, epilepsy, and psychiatric disorders. Here we give an overview of relevant nasal anatomy and physiology and discuss the pathways and mechanisms likely involved in drug transport from the nasal epithelium to the CNS. Finally we review both pre-clinical and clinical studies involving intranasal delivery of biologics to the CNS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Administration, Intranasal
  • Animals
  • Biological Products / administration & dosage*
  • Biological Products / metabolism
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism*
  • Central Nervous System Diseases / drug therapy*
  • Central Nervous System Diseases / metabolism
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Humans


  • Biological Products