Direct transport theory: From the nose to the brain

Dhas, Namdev; Yadav, Dattatray; Singh, Ashutosh; Garkal, Atul; Kudarha, Ritu; Bangar, Priyanka; Savjani, Jignasa; Pardeshi, Chandrakantsing V.; Garg, Neha; Mehta, Tejal

doi:10.1016/b978-0-12-822522-6.00001-1

Cited by 4 publications

(1 citation statement)

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“…12 The general concept of intranasal drug delivery is based on the premise that this noninvasive route of administration may employ, at least in part, direct nose-to-brain transport, which avoids rapid drug metabolism by the liver, circumvents drug rejection by the blood-brain barrier (BBB), and minimizes the need for flooding the entire systemic circulation with drug to deliver sufficiently high drug levels to the brain lesion. 13,14 It has remained unclear, however, whether the intranasal route of POH/NEO100 administration is indeed able to achieve its key objective, namely to enable the drug to reach its intended intracerebral tumor target. Such confirmation is critical because it will lend much-needed support to the model that intranasal NEO100 represents a viable, safer, and potentially superior means of treating patients with brain cancer.…”

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Detection of perillyl alcohol and its metabolite perillic acid in postsurgical glioblastoma tissue after intranasal administration of NEO100: illustrative case

Schönthal

Swenson

Bonney

et al. 2022

Journal of Neurosurgery: Case Lessons

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BACKGROUND Intranasal delivery of NEO100, a pharmaceutical-grade version of the natural monoterpene perillyl alcohol (POH), is undergoing clinical phase IIa testing as a treatment for glioblastoma (GBM). However, so far there is no evidence that intranasal delivery of NEO100 indeed results in POH reaching intracranial malignancies in a patient. OBSERVATIONS After surgical removal of her recurrent GBM tumor, a patient received daily intranasal NEO100 therapy for more than 3 years before a second recurrence emerged. At that time, a final dose of NEO100 was given shortly before the tumor tissue was surgically removed, and the tissue was processed for high-performance liquid chromatography analysis of POH and its primary metabolite, perillic acid (PA). Both molecules could readily be detected in the tumor tissue. LESSONS This is the first demonstration of POH and PA in brain tumor tissue from any patient. It reveals that intranasal administration of NEO100 is a valid approach to achieve delivery of this agent to a brain tumor. In view of the noninvasive and safe nature of this method, along with tentative indications of activity, our findings add confidence to the notion that intranasal administration of NEO100 holds potential as a new treatment option for brain-localized malignancies.

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confidence: 99%