2019
DOI: 10.1007/s11095-019-2613-8
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Direct Drug Delivery of Low-Permeable Compounds to the Central Nervous System Via Intranasal Administration in Rats and Monkeys

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Cited by 24 publications
(16 citation statements)
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“…In contrast, the intranasal route provides a direct and noninvasive pathway to bypass the BBB, with increased intracerebral drug concentrations, decreased quantities, and few side effects observed 44 . Several proteins and polypeptides, such as BDNF and CNTF, have been reported that can efficiently enter the CNS target location through the intranasal route in a mouse model, 45 and it has also been demonstrated that the intranasal administration route could increase the delivery of low-permeable small molecules to the brain in both rats and monkeys, 46 and also to be effective in EcoHIV-infected mice and voluntary AD patients 47 , 48 . Although carrier and intrusive issues still need to be addressed, direct nose-to-brain drug delivery offers a potentially efficient strategy for AD treatment 44 .…”
Section: Discussionmentioning
confidence: 99%
“…In contrast, the intranasal route provides a direct and noninvasive pathway to bypass the BBB, with increased intracerebral drug concentrations, decreased quantities, and few side effects observed 44 . Several proteins and polypeptides, such as BDNF and CNTF, have been reported that can efficiently enter the CNS target location through the intranasal route in a mouse model, 45 and it has also been demonstrated that the intranasal administration route could increase the delivery of low-permeable small molecules to the brain in both rats and monkeys, 46 and also to be effective in EcoHIV-infected mice and voluntary AD patients 47 , 48 . Although carrier and intrusive issues still need to be addressed, direct nose-to-brain drug delivery offers a potentially efficient strategy for AD treatment 44 .…”
Section: Discussionmentioning
confidence: 99%
“…Intranasal administration is an attractive route for drug delivery to the brain because it allows the direct transport of drugs from the nasal cavity to the brain parenchyma by bypassing systemic circulation [3][4][5][6][7][8]. This strategy has been called "nose-to-brain delivery".…”
Section: Introductionmentioning
confidence: 99%
“…Thus, in a study with rabbits and rats, intranasal administration of diazepam in a microemulsion formulation produced a homogenous drug distribution in the brain with concentrations in the olfactory bulb no greater than those in other brain regions or the brain as a whole [32]. In a separate study in rats, the relative exposure of midazolam in the olfactory bulb and olfactory tract following intranasal deposition of an aqueous suspension of midazolam was no different from the relative exposure in the rest of the brain, and the ratio of exposures following intranasal and intravenous delivery in the olfactory areas did not substantially exceed the ratio in the rest of the brain [28]. These results indicate minimal brain-to-nose delivery of the highly lipophilic benzodiazepines; the bulk of distribution to the brain is via the venous circulation.…”
Section: Discussionmentioning
confidence: 82%