Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease

被引:517
作者
Hanson, Leah R. [1 ]
Frey, William H., II [1 ,2 ]
机构
[1] HealthPartners Res Fdn, Reg Hosp, Alzheimers Res Ctr, St Paul, MN 55101 USA
[2] Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA
关键词
D O I
10.1186/1471-2202-9-S3-S5
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Intranasal delivery provides a practical, non-invasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal cord. This technology allows drugs that do not cross the BBB to be delivered to the central nervous system within minutes. It also directly delivers drugs that do cross the BBB to the brain, eliminating the need for systemic administration and its potential side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and external environment. Intranasal delivery does not necessarily require any modification to therapeutic agents. A wide variety of therapeutics, including both small molecules and macromolecules, can be targeted to the olfactory system and connected memory areas affected by Alzheimer's disease. Using the intranasal delivery system, researchers have reversed neurodegeneration and rescued memory in a transgenic mouse model of Alzheimer's disease. Intranasal insulin-like growth factor-1, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models. Intranasal delivery has been used to target the neuroprotective peptide NAP to the brain to treat neurodegeneration. Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown to stimulate neurogenesis in adult animals. Intranasal insulin improves memory, attention, and functioning in patients with Alzheimer's disease or mild cognitive impairment, and even improves memory and mood in normal adult humans. This new method of delivery can revolutionize the treatment of Alzheimer's disease, stroke, and other brain disorders.
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