Treating mental illness via novel nasal-spray technology

Oxytocin is a neuropeptide made in the brain that plays a critical role in female reproductive functions, facilitating childbirth and breastfeeding. It also has been shown to have effects on behavior, both amorous, for which it has been dubbed the "love hormone," and in more general social interactions. The chemical's effect on social behavior has led researchers at Norway's Institute of Clinical Medicine (Oslo) to test its potential for treating mental illness. They are using a new intranasal drug-delivery device developed by OptiNose, also headquartered in Oslo with offices in Yardley, PA, and in the United Kingdom, which enables low doses of the hormone to be administered deep within the nasal cavity.

In tests on 16 healthy male volunteers, research showed that only low doses of oxytocin produced an effect on perception of social signals, according to Ole A. Andreassen, MD, PhD, Professor, NORMENT - KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. He co-authored a paper on the subject in Translational Psychiatry. High doses could, in fact, exacerbate the condition, researchers say.

As part of the test, some volunteers received the hormone intravenously, which had no effect, say researchers. "This indicates that intranasally administered oxytocin travels directly to the brain, as we have long believed," says Andreassen. Oxytocin is a relatively large molecule that has difficulty permeating the blood-brain barrier, making nasal administration the preferred drug-delivery method, and OptiNose the preferred technology.

OptiNose has developed a patented technology, which it calls a Bi-Directional Breath Powered drug-delivery system, that uses the natural functions of a patient's breath to deliver medications beyond the nasal valve deep into targeted areas of the nasal cavity. The user exhales into the device, naturally closing the soft palate and sealing off the nasal cavity from the throat, explains the company. The exhaled breath carries medication from the device into one side of the nose through a specially shaped sealing nosepiece, balancing the pressure across the soft palate. Narrow nasal passages are gently expanded and medication is transported well beyond the nasal valve to targeted sites. After delivering medication to the targeted sites, air flows around to the opposite side of the nasal cavity and exits through the other side of the nose rather than into the throat or lungs.

The company has successfully licensed a first product using this technology for migraine treatment to Avanir in North America (which has since been acquired by Otsuka Pharmaceutical Co., Ltd.), and it has reported clinical success with other products, including one that is in development for chronic nasal inflammatory diseases.

Per Djupesland, MD, PhD, inventor of the technology and a co-founder of OptiNose, declined to disclose any details involving the materials used in the device or its design. "The nasal delivery devices for liquids and powders are based on proprietary technology and design. We do have a number of peer-reviewed  publications on nasal deposition studies and from our Phase 1 to 3 trials that can be accessed on our website," he told PlasticsToday.

Researchers have been searching for a way to get improved and more reliable brain activity with many medications, including oxytocin to treat conditions such as autism and schizophrenia, and a variety of other drugs for treatment of Alzheimer's and other brain diseases, explains Andreassen. "The OptiNose technology significantly changes the way drug is delivered high up in the nose, and may be the drug-delivery solution we've been looking for. If we can improve social cognition in healthy people with low-dose oxytocin, then we may be able to address a core symptom suffered by millions of patients worldwide with autism," says Andreassen.

Andreassen and his colleagues are now running tests in volunteers diagnosed with autism spectrum disorders. "We hope that this research project is the first step in the development of a series of new medicines that may be of great help to more people with mental illness, Andreassen adds.