Intranasal administration of progesterone: A potential efficient route of delivery for cerebroprotection after acute brain injuries. (February 2019)

• Record Type: Journal Article
• Authors: Guennoun, Rachida; Fréchou, Magalie; Gaignard, Pauline; Liere, Philippe; Slama, Abdelhamid; Schumacher, Michael; Denier, Christian; Mattern, Claudia
• Is Part Of: Neuropharmacology. Volume 145(2019)Part B
• Page Start: 283
• Page End: 291
• Publication Date: 2019-02
• Subjects: Drug delivery -- Nasal -- Route of administration -- Stroke -- Traumatic brain injury -- Steroid; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2018.06.006
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Progesterone has been shown to be cerebroprotective in different experimental models of brain injuries and neurodegenerative diseases. The preclinical data provided great hope for its use in humans. The failure of Phase 3 clinical trials to demonstrate the cerebroprotective efficiency of progesterone in traumatic brain injury (TBI) patients emphasizes that different aspects of the design of both experimental and clinical studies should be reviewed and refined. One important aspect to consider is to test different routes of delivery of therapeutic agents. Several studies have shown that the intranasal delivery of drugs could be used in different experimental models of central nervous system diseases. In this review, we will summarize the pharmacokinetic characteristics and practical advantages of intranasal delivery of progesterone. A special emphasis will be placed on describing and discussing our recent findings showing that intranasal delivery of progesterone after transient focal cerebral ischemia: 1) improved motor functions; 2) reduced infarct volume, neuronal loss, blood brain barrier disruption; and 3) reduced brain mitochondrial dysfunctions. Our data suggest that intranasal delivery of progesterone is a potential efficient, safe and non-stressful mode of administration that warrants evaluation for cerebroprotection in patients with brain injuries. This article is part of the Special Issue entitled "Novel Treatments for Traumatic Brain Injury". Highlights: Progesterone is cerebroprotective in experimental models of brain injuries. Promise of Phase II and failure of Phase III clinical TBI trials using progesterone. Intranasal delivery of drugs to the brain: advantages and mechanisms. Intranasal delivery of progesterone to brain: formulation and pharmacokinetics. High therapeutic potential of intranasal delivery of progesterone to brain.