title: Intranasal delivery: circumventing the iron curtain to treat neurological disorders.
abstract: BACKGROUND
  The blood-brain barrier (BBB) is like an iron curtain that prevents exogenous substances, including most drugs, from entering the CNS. Intranasal delivery has been demonstrated to circumvent the BBB due to the special anatomy of the olfactory and trigeminal neural pathways that connect the nasal mucosa with the brain and the perivascular pathway within the CNS. In the last two decades, the concepts, mechanisms and pathways of intranasal delivery to the CNS have led to great success both in preclinical and clinical studies. More researchers have translated results from bench to bedside, and a number of publications have reported the clinical application of intranasal delivery.
  
  
  METHODS
  This review summarizes results from recent clinical trials utilizing intranasal delivery of therapeutics to explore its pharmacokinetics and application to treating neurological disorders. Moreover, existing problems with the methods and possible solutions have also been discussed. The promising results from clinical trials have demonstrated that intranasal delivery provides an extraordinary approach for circumventing the BBB. Many drugs, including high-molecular-weight molecules, could potentially improve the treatment of neurological disorders via intranasal administration.
  
  
  CONCLUSIONS
  Intranasal delivery is a novel method with great potential for delivering and targeting therapeutics to the CNS to treat neurological disorders.
authors.affiliation: a Department of Neurology, Jinling Hospital, Medical School of Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China +86 25 8086 0124 ; +86 25 8466 4563 ; xfliu2@vip.163.com.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: a Department of Neurology, Jinling Hospital, Medical School of Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China +86 25 8086 0124 ; +86 25 8466 4563 ; xfliu2@vip.163.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Neurology, Jinling Hospital, Medical School of Nanjing University , 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China +86 25 8086 0124 ; +86 25 8466 4563 ; xfliu2@vip.163.com.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
mesh_terms: D000281:Administration, Intranasal; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D009297:Nasal Mucosa / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D014276:Trigeminal Nerve / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations
keywords: clinical trial; intranasal delivery; neurological disorders