Uchegbu, I;
Wang, Z;
Xiong, G;
Tsang, A;
Schatzlein, A;
(2019)
Nose to brain delivery.
Journal of Pharmacology and Experimental Therapeutics
, 370
(3)
pp. 593-601.
10.1124/jpet.119.258152.
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Abstract
The global prevalence of neurological disorders is rising and yet we are still unable to deliver most drug molecules, in therapeutic quantities, to the brain. The blood brain barrier, consists of a tight layer of endothelial cells surrounded by astrocyte foot processes and these anatomical features constitute a significant barrier to drug transport from the blood to the brain. One way to bypass the BBB and thus treat diseases of the brain is to use the nasal route of administration and deposit drugs at the olfactory region of the nares; from where they travel to the brain via mechanisms that are still not clearly understood; with travel across nerve fibres and travel via a perivascular pathway both being hypothesized. The nose to brain route has been demonstrated repeatedly in preclinical models, with both solution and particulate formulations. The nose to brain route has also been demonstrated in human studies with solution and particle formulations. The entry of device manufacturers into the arena will enable the benefits of this delivery route to become translated into approved products. The key factors which determine the efficacy of delivery via this route include: delivery to the olfactory area of the nares as opposed to the respiratory region, a longer retention time at the nasal mucosal surface, penetration enhancement of the active through the nasal epithelia and a reduction in drug metabolism in the nasal cavity. Indications where nose to brain products are likely to emerge first include: neurodegeneration, post-traumatic stress disorder, pain and glioblastoma.
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