Intranasal delivery of biologics to the central nervous system

被引:825
作者
Lochhead, Jeffrey J. [1 ]
Thorne, Robert G. [1 ,2 ,3 ,4 ]
机构
[1] Univ Wisconsin, Madison Sch Pharm, Div Pharmaceut Sci, Madison, WI 53705 USA
[2] Ctr Neurosci, New York, NY USA
[3] Neurosci Training Program, Iowa City, IA USA
[4] Univ Wisconsin Madison, Clin Neuroengn Training Program, Madison, WI 53706 USA
关键词
Drug delivery; Nasal passage; Olfactory; Trigeminal; Proteins; Gene vectors; Stem cells; BLOOD-BRAIN-BARRIER; GROWTH-FACTOR-I; REDUCES INFARCT VOLUME; GALANIN-LIKE PEPTIDE; OLFACTORY EPITHELIUM; NASAL-MUCOSA; TAU-HYPERPHOSPHORYLATION; HORSERADISH-PEROXIDASE; ELECTRICAL-RESISTANCE; ALZHEIMERS-DISEASE;
D O I
10.1016/j.addr.2011.11.002
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (c) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:614 / 628
页数:15
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