Abstract
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-I, 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.
Highlights
The use of intranasal (IN) administration to target therapeutics to the central nervous system (CNS) has many benefits in the treatment of neurologic disorders
Intranasal insulin-like growth factor-I, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models
Noninvasive IN delivery targets therapeutics to the CNS, reducing systemic exposure and side effects; this can be advantageous for delivery of many CNS therapeutics, including those that can cross the blood-brain barrier (BBB) upon systemic administration
Summary
The use of intranasal (IN) administration to target therapeutics to the central nervous system (CNS) has many benefits in the treatment of neurologic disorders. Memory is improved by intranasal insulin treatment IN insulin improves memory in normal adults and patients with Alzheimer's disease without altering blood glucose. Ability to deliver insulin to the CNS without altering blood glucose could provide an effective means to improve glucose uptake and utilization, and reduce cognitive deficits in patients with memory disorders. Using the IN delivery method to target insulin to the CNS originally developed by Frey [28], Born and coworkers [29] demonstrated that cerebrospinal fluid insulin levels significantly increased after treatment of normal adults with insulin, with no change in blood levels of insulin. IN treatment with insulin for 8 weeks improved memory (delayed recall of words) and mood at doses that did not alter blood levels of insulin or glucose [30]. Longer treatment with IN insulin (21 days) enhanced memory, attention, and functioning compared with placebo in patients with either early stage Alzheimer's disease or mild cognitive impairment [33,34]
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