Intranasal Administration of Milnacipran in Rats: Evaluation of the Transport of Drugs to the Systemic Circulation and Central Nervous System and the Pharmacological Effect

Uchida, Masaki; Katoh, Takuya; Mori, Mutsuhiro; Maeno, Takuya; Ohtake, Kazuo; Kobayashi, Jun; Morimoto, Yasunori; Natsume, Hideshi

doi:10.1248/bpb.34.740

Cited by 18 publications

(12 citation statements)

References 32 publications

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“…Intranasal administration is a promising route for delivering drugs effectively to the brain across the BBB [36, 37]. This strategy has been widely applied to deliver therapeutic drugs to the central nervous system as it is associated with fewer systemic effects [16, 38, 39]. Drugs administered intranasally can be transported directly from the nasal mucosa to the brain along the cranial nerves [37].…”

Section: Discussionmentioning

confidence: 99%

“…Intranasal administration is also a promising route of administration due to its higher direct delivery to the brain relative to peroral administration, intraduodenal injection or jugular vein injection [39]. Our data also showed that brain iron content was increased obviously using the transnasal delivery system, and that the delivery efficiency of FAC-LIP is higher than that of FAC, demonstrating that liposome encapsulation is an effective vehicle and intranasal administration is an efficiency and convenient method for iron delivery to the brain.…”

Section: Discussionmentioning

confidence: 99%

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Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

et al. 2017

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BackgroundIron deficiency in children can have significant neurological consequences, and iron supplementation is an effective treatment of choice. However, traditional routes of iron supplementation do not allow efficient iron delivery to the brain due to the presence of the blood–brain barrier. So an easily delivered iron formulation with high absorption efficiency potentially could find widespread application in iron deficient infants.ResultsIn this study, we have developed and characterized a nanovesicular formulation of ferric ammonium citrate (ferric ammonium citrate nanoliposomes, FAC-LIP) and have shown that it can increase brain iron levels in rats following nasal administration. FAC was incorporated into liposomes with high efficiency (97%) and the liposomes were small (40 nm) and stable. Following intranasal delivery in rats, FAC-LIP significantly increased the iron content in the olfactory bulb, cerebral cortex, striatum, cerebellum and hippocampus, and was more efficient at doing so than FAC alone. No signs of apoptosis or abnormal cell morphology were observed in the brain following FAC-LIP administration, and there were no significant changes in the levels of SOD and MDA, except in the cerebellum and hippocampus. No obvious morphological changes were observed in lung epithelial cells or tracheal mucosa after nasal delivery, suggesting that the formulation was not overtly toxic.ConclusionsIn this study, nanoscale FAC-LIP proved an effective system delivering iron to the brain, with high encapsulation efficiency and low toxicity in rats. Our studies provide the foundation for more detailed investigations into the applications of niosomal nasal delivery of liposomal formulations of iron as a simple and safe therapy for iron deficiency anemia.Graphical abstractThe diagrammatic sketch of “Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain”. Nanoliposome-encapsulated ferric ammonium citrate (FAC-LIP) was successfully prepared and intranasal administration of FAC-LIP increased both the total iron contents and iron storage protein (FTL) expression in rat olfactory bulb, cerebral cortex, striatum and hippocampus, compared with those of FAC groups. Moreover, there was not overtly toxic affects to brain, lung epithelial cells and tracheal mucosa. Electronic supplementary materialThe online version of this article (doi:10.1186/s12951-017-0277-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

et al. 2017

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Section: Glutathionementioning

confidence: 99%

“…It has long been studied as a means to achieve central nervous system effects and has been studied for multiple agents in an effort to treat diseases such as depression, schizophrenia, Alzheimer's and Parkinson's disease [144]. Medications administered intranasally have reportedly been detected in the cerebrospinal fluid (CSF) as fast as 1 minute after delivery [144]. Intranasal administration of neuropeptides has been studied and found to have the advantage of bypassing the blood-brain barrier, which has served to limit the effectiveness of systemic therapies on central nervous system (CNS) symptoms.…”

Section: Glutathionementioning

confidence: 99%

“…In a recent survey study of 70 patients who had used intranasal glutathione for conditions that included multiple chemical sensitivity, allergies/sinusitis, Parkinson's disease, Lyme disease, fatigue, and other symptoms, over 86% of the respondents found intranasal glutathione nasal spray to be comfortable and easy to use and 62.1% reported experiencing health benefits while 12.1% of respondents reported having experienced adverse effects, the most common of which were irritation of nasal passages, headache and bloody nose [146]. A recent rat study of intranasal milnacipran, a serotonin noradrenaline reuptake inhibitor used for depression and fibromyalgia, found both CSF and systemic levels of the drug to be higher when administered intranasally compared to orally and demonstrated an increased antidepressant effect from the transnasal administration [144]. There is evidence for carrier-mediated transport of glutathione across the blood-brain barrier in rats administered GSH via carotid artery catheterization [147] and in other animal models [148].…”

Section: Glutathionementioning

confidence: 99%

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A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water‐Damaged Buildings, Mold, and Mycotoxins

Hope

2013

The Scientific World Journal

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Physicians are increasingly being asked to diagnose and treat people made ill by exposure to water-damaged environments, mold, and mycotoxins. In addition to avoidance of further exposure to these environments and to items contaminated by these environments, a number of approaches have been used to help persons affected by exposure to restore their health. Illness results from a combination of factors present in water-damaged indoor environments including, mold spores and hyphal fragments, mycotoxins, bacteria, bacterial endotoxins, and cell wall components as well as other factors. Mechanisms of illness include inflammation, oxidative stress, toxicity, infection, allergy, and irritant effects of exposure. This paper reviews the scientific literature as it relates to commonly used treatments such as glutathione, antioxidants, antifungals, and sequestering agents such as Cholestyramine, charcoal, clay and chlorella, antioxidants, probiotics, and induced sweating.

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Nose as a Route for Drug Delivery

Serralheiro

Alves

Sousa

et al. 2013

Nasal Physiology and Pathophysiology of Nasal Disorders

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Intranasal Administration of Milnacipran in Rats: Evaluation of the Transport of Drugs to the Systemic Circulation and Central Nervous System and the Pharmacological Effect

Cited by 18 publications

References 32 publications

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

Nasal delivery of nanoliposome-encapsulated ferric ammonium citrate can increase the iron content of rat brain

A Review of the Mechanism of Injury and Treatment Approaches for Illness Resulting from Exposure to Water‐Damaged Buildings, Mold, and Mycotoxins

Nose as a Route for Drug Delivery

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