Direct nose to brain drug delivery<i>via</i>integrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting

Pardeshi, Chandrakantsing V.; Belgamwar, Veena S.

doi:10.1517/17425247.2013.790887

Cited by 388 publications

(220 citation statements)

References 73 publications

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“…The extracellular transportation is a rapid process which is permitted to occur only few minutes within olfactory cells (39). In contrast, the intracellular transport mechanism is a slow process and lasts for over several hours by axonal transportation (40).…”

Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Zhang

Meng

Zhou

et al. 2015

AAPS J

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Abstract. Exendin-4 is now considered as a promising drug for the treatment of cerebral ischemia. To determine the neuroprotective effects of intranasal exendin-4, C57BL/6J mice were intranasally administered with exendin-4 daily for 7 days before middle cerebral artery occlusion (MCAO) surgery. Intranasally administered exendin-4 produced higher brain concentrations and lower plasma concentrations when compared to identical doses administered interperitoneally. Neurological deficits and volume of infarcted lesions were analyzed 24 h after ischemia. Intranasal administration of exendin-4 exhibited significant neuroprotection in C57BL/6 mice subjected to MCAO by reducing neurological deficit scores and infarct volume. The neuroprotective effects of exendin-4 were blocked by the knockdown of GLP-1R with shRNA. However, exendin-4 has no impact on glucose and insulin levels which indicated that the neuroprotective effect was mediated by the activation of GLP-1R in the brain. Exendin-4 intranasal administration restored the balance between pro-and anti-apoptotic proteins and decreased the expression of Caspase-3. The anti-apoptotic effect was mediated by the cAMP/PKA and PI3K/Akt pathway. These findings provided evidence that exendin-4 intranasal administration exerted a neuroprotective effect mediated by an anti-apoptotic mechanism in MCAO mice and protected neurons against ischemic injury through the GLP-1R pathway in the brain. Intranasal delivery of exendin-4 might be a promising strategy for the treatment of ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Zhang

Meng

Zhou

et al. 2015

AAPS J

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“…Nasal cavity irradiation is convenient and causes no injury. It is reported that drugs absorbed by nasal mucosa can be easily transported to the brain, 32 and intranasal route is the alternative route to parenteral administration. 33 Nasal cavity irradiation helps CNT go across the BBB and brings better central analgesic effects.…”

Section: Analgesic Effects Of the Cnt Nanocapsulesmentioning

confidence: 99%

Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its central analgesic effects under red light

Yang

Zhao

et al. 2017

IJN

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Cobra neurotoxin (CNT), a peptide isolated from snake venom of Naja naja atra , shows central analgesic effects in our previous research. In order to help CNT pass through blood–brain barrier (BBB) and improve its central analgesic effects, a new kind of CNT nanocapsules were prepared by double emulsification with soybean lecithin and cholesterol as the shell, and pheophorbide as the photosensitizer added to make it photoresponsive. The analgesic effects were evaluated by hot plate test and acetic acid-induced writhing in mice. The CNT nanocapsules had an average particle size of 229.55 nm, zeta potential of −53.00 mV, encapsulation efficiency of 84.81% and drug loading of 2.98%, when the pheophorbide content was 1% of lecithin weight. Pheophorbide was mainly distributed in outer layer of the CNT nanocapsules and increased the release of the CNT nanocapsules after 650 nm illumination. The central analgesic effects were improved after intraperitoneal injection of CNT at 25 and 50 µg·kg −1 under 650 nm irradiation for 30 min in the nasal cavity. Activation of pheophorbide by red light generated reactive oxygen species which opened the nanocapsules and BBB and helped the CNT enter the brain. This research provides a new drug delivery for treatment of central pain.

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“…Thus, the trigeminal pathway, which is often overlooked by the researchers, can be an important direct pathway of drug delivery to the brain. [16,17,18,19] Three branches of the trigeminal nerve (ophthalmic division, maxillary division, and mandibular division) merge at the trigeminal ganglion, enter the CNS in the pons, and terminate in the spinal trigeminal nuclei in the brainstem. Therefore, cross-talk between the trigeminal and olfactory routes of brain drug delivery is possible.…”

Section: Pathways For Reaching the Drug To Brain After Intranasal Admmentioning

confidence: 99%

Nasal Drug Delivery System: A Route for Braine Targetting

Jadhav¹

2017

WJPR

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Present review highlights the potential of nasal mucosa as an administration route for targeting the central nervous system, the brain.Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of medication in the remaining tissues. Thus improving efficacy of the drug and reducing side effects. The nasal mucosa when compared to other mucous membranes is easily accessible and provides a practical entrance portal for small and large molecules. Intranasal administration offers rapid onset of action, no first-pass effect, no gastrointestinal degradation or lung toxicity and non-invasiveness application and also improves bioavailability. It is thought that olfactory route of drug transport, by pass the blood-brain barrier and allows the direct transport of drug from the nose to the brain. This review provides an overview of strategies to improve the drug delivery to brain via nasal mucosa and recent advances in this field.

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Direct nose to brain drug deliveryviaintegrated nerve pathways bypassing the blood–brain barrier: an excellent platform for brain targeting

Cited by 388 publications

References 73 publications

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Intranasal Delivery of Exendin-4 Confers Neuroprotective Effect Against Cerebral Ischemia in Mice

Photoresponsive nanocapsulation of cobra neurotoxin and enhancement of its central analgesic effects under red light

Nasal Drug Delivery System: A Route for Braine Targetting

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