title: The blood-brain barrier and nasal drug delivery to the central nervous system.
abstract: BACKGROUND
  The blood-brain barrier (BBB) is a highly efficient system that separates the central nervous system (CNS) from general circulation and promotes selective transport of molecules that are essential for brain function. However, it also limits the distribution of systemically administered therapeutics to the brain; therefore, there is a restricted number of drugs available for the treatment of brain disorders. Several drug-targeting strategies have been developed to attempt to bypass the BBB, but none has proved sufficiently effective in reaching the brain.
  
  
  METHODS
  The objective of this study is to generally review these strategies of drug administration to the CNS.
  
  
  RESULTS
  Noninvasive methods of drug delivery, such as chemical and biologic transport systems, do not represent a feasible platform, whereas for most drugs, it is still not possible to achieve therapeutic levels within the brain tissue after intravenous or oral administration, and the use of higher potency or more concentrated doses may cause serious toxic side effects. Direct intrathecal drug delivery through a catheter into the CNS also presents several problems. Intranasal drug delivery is a potential alternative method due to the direct transport into the cerebrospinal fluid (CSF) compartment along the olfactory pathway, but the study's conclusions are controversial. An endoscopic intranasal surgical procedure using established skull base surgery reconstruction techniques based on the use of a nasal mucosa surgical flap as the only obstacle between the nose and the subarachnoid space has appeared as a potential solution to increase the absorption of intranasal drugs to the CNS.
  
  
  CONCLUSIONS
  Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.
authors.affiliation: Department of Otolaryngology, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Marcel Menon
authors.initials: MM
authors.lastname: Miyake
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Bleier
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001927:Brain Diseases / Q000188:drug therapy*; D002490:Central Nervous System / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods*; D004724:Endoscopy; D006801:Humans; D009297:Nasal Mucosa / Q000601:surgery; D009833:Olfactory Pathways / Q000502:physiology / Q000601:surgery; D019651:Plastic Surgery Procedures; D019291:Skull Base / Q000601:surgery; D013346:Subarachnoid Space / Q000187:drug effects* / Q000601:surgery; D013524:Surgical Flaps / Q000706:statistics & numerical data*