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The intranasal route of administration has been preferred for dosing POH in early-stage clinical trials associated with promising outcomes in primary brain cancer. However, it is unclear how intranasal POH targets brain tumors in these patients. Multiple studies indicate that intranasally applied large molecules may enter the brain and cerebrospinal fluid (CSF) through direct olfactory and trigeminal nerve-associated pathways originating in the nasal mucosa that bypass the blood\u2013brain barrier. It is unknown whether POH, a small molecule subject to extensive nasal metabolism and systemic absorption, may also undergo direct transport to brain or CSF from the nasal mucosa. Here, we compared CSF and plasma concentrations of POH and its metabolite, perillic acid (PA), following intranasal or intravascular POH application. Samples were collected over 70\u00a0min and assayed by high-performance liquid chromatography. Intranasal administration resulted in tenfold higher CSF-to-plasma ratios for POH and tenfold higher CSF levels for PA compared to equal dose intravascular administration. Our preclinical results demonstrate POH undergoes direct transport from the nasal mucosa to the CSF, a finding with potential significance for its efficacy as an intranasal chemotherapeutic for brain cancer.<\/jats:p>","DOI":"10.1038\/s41598-021-85293-4","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T12:47:41Z","timestamp":1616071661000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Intranasal administration of the chemotherapeutic perillyl alcohol results in selective delivery to the cerebrospinal fluid in rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Geetika","family":"Nehra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan","family":"Rettig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Gould","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill D.","family":"Haag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert G.","family":"Thorne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"issue":"1\u20132","key":"85293_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijpharm.2007.03.025","volume":"337","author":"HR Costantino","year":"2007","unstructured":"Costantino, H. 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Dr. Michael Gould serves as a scientific advisor for NeOnc Technologies, Inc. (NTI), an early-stage cancer biotechnology company that developed NEO100 (a novel, highly purified form of perillyl alcohol). Dr. Robert Thorne is employed full-time as a Denali Fellow at Denali Therapeutics Inc., a for-profit biotechnology company focused on the discovery and development of therapies for patients with neurodegenerative diseases. Dr. Thorne is also appointed as an Adjunct Associate Professor in the Department of Pharmaceutics, University of Minnesota-Twin Cities. The authors declare that this research was conducted in the absence of commercial or financial relationships that could be construed as a potential conflict of interest. Dr. Geetika Nehra, Dr. Shannon Andrews, Dr. Jill Haag, and Ms. Joan Rettig have no competing interests to declare.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"6351"}}