The Blood-Brain Barrier and Nasal Drug Delivery to the Central Nervous System

Miyake, Marcel M.; Bleier, Benjamin S.

doi:10.2500/ajra.2015.29.4149

Cited by 83 publications

(45 citation statements)

References 67 publications

(107 reference statements)

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“…In humans and nonhuman primates, drug delivered into the nasal cavity is primarily deposited in the respiratory zone located between the inferior and middle turbinate, and is absorbed into the systemic circulation (Pires et al, 2009;Grassin-Delyle et al, 2012). Some lines of research have suggested that IN drug administration may permit direct absorption to the brain that circumvents the blood-brain barrier (Dhuria et al, 2010;Johnson et al, 2010;Miyake and Bleier, 2015).…”

Section: Introductionmentioning

confidence: 99%

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Saccone

Lindsey

Koeppe

et al. 2016

J Pharmacol Exp Ther

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The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [11 C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys.

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Section: Introductionmentioning

confidence: 99%

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Saccone

Lindsey

Koeppe

et al. 2016

J Pharmacol Exp Ther

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“…4,318,319 The intranasal route plays a role in overcoming the BBB and targeting the drugs directly to the brain. 282,[319][320][321][322][323][324][325] However, the oral, dermal, and intravenous routes can be used to administration of nanodevices …”

Section: Remarks and Challengesmentioning

confidence: 99%

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

Fonseca-Santos¹,

Chorilli²,

Gremião³

2015

IJN

247

160

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Alzheimer’s disease is a neurological disorder that results in cognitive and behavioral impairment. Conventional treatment strategies, such as acetylcholinesterase inhibitor drugs, often fail due to their poor solubility, lower bioavailability, and ineffective ability to cross the blood–brain barrier. Nanotechnological treatment methods, which involve the design, characterization, production, and application of nanoscale drug delivery systems, have been employed to optimize therapeutics. These nanotechnologies include polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, microemulsion, nanoemulsion, and liquid crystals. Each of these are promising tools for the delivery of therapeutic devices to the brain via various routes of administration, particularly the intranasal route. The objective of this study is to present a systematic review of nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease.

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“…In their review, Miyake and Bleier discuss the challenges of formulating drug targeting strategies to bypass the blood-brain barrier and deliver therapeutics to the central nervous system (CNS). 12 The authors describe the innovative use of endoscopic grafting techniques to facilitate drug administration to the subarachnoid space via an intranasal route. 12 A nasal mucosal surgical flap is created employing established skull base reconstruction methods to serve as a vehicle for pharmaceutical delivery to the CNS.…”

mentioning

confidence: 99%

“…12 The authors describe the innovative use of endoscopic grafting techniques to facilitate drug administration to the subarachnoid space via an intranasal route. 12 A nasal mucosal surgical flap is created employing established skull base reconstruction methods to serve as a vehicle for pharmaceutical delivery to the CNS. 12 As more advanced endoscopic skull base procedures are developed, it is important to assess the clinical outcomes of such surgeries.…”

mentioning

confidence: 99%

“…12 A nasal mucosal surgical flap is created employing established skull base reconstruction methods to serve as a vehicle for pharmaceutical delivery to the CNS. 12 As more advanced endoscopic skull base procedures are developed, it is important to assess the clinical outcomes of such surgeries. In their study, Deckard et al track QOL measures following endoscopic resection of sinonasal and skull base neoplasms.…”

mentioning

confidence: 99%

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Editorial: New Perspectives in the Pathogenesis and Management of Rhinologic and Allergic Airway Disease

Lee¹

2015

Am J Rhinol�Allergy

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for their continued support and outstanding leadership. The AJRA is committed to presenting the latest and highest quality clinical and translational research in the fields of rhinology, allergy, and skull base pathology. To that end, the March/April issue of the AJRA encompasses a broad spectrum of studies offering novel perspectives on a variety of allergy and rhinology related topics.Since its characterization, much knowledge has been gained regarding the multifaceted inflammatory nature of chronic rhinosinusitis (CRS), with both host (i.e., allergy, immunodeficiency, anatomic obstruction, etc.) and environmental factors (i.e., bacterial/viral infections, biofilms, pollutants, etc.) understood to be involved in its pathogenesis. 1 However, despite extensive research efforts, no clear etiology for CRS has been delineated. 1 In this issue, several studies aim to deepen our understanding of the complex pathophysiology of CRS and provide further insight into new treatment alternatives for this disease entity.On a molecular level, Lawrence et al investigate the effects of superoxide dismutase (SOD) on fungal antigen induced inflammatory responses in human sinonasal epithelial cells (HSNECs). 2 SOD treatment of HSNECs derived from CRS with nasal polyp patients attenuated inflammation triggered by Aspergillus and Alternaria, suggesting that SOD could be used as a potential therapeutic option for CRS in the future. 2 From a clinical aspect, Stevens and Peters examine how underlying immunodeficiencies may contribute to CRS. 3 In their review, multiple immune disorders (i.e., common variable immunodeficiency, selective IgA deficiency, and specific antibody deficiencies) are discussed including appropriate diagnosis, treatment, and impact on CRS. 3 Timely management of such immunodeficiencies with immunoglobulin replacement, etc. may have beneficial effects on the clinical course of CRS, particularly in patients with refractory disease. Likewise, Sedaghat and colleagues explore clustering patterns of CRS symptoms to determine correlations with demographic characteristics, comorbidities, and other objective findings. 4 Such unique associations indicate that distinct pathophysiologic processes may be responsible for specific CRS symptomatology.Endoscopic sinus surgery (ESS) plays an integral role in the surgical therapy of CRS, with well-documented benefits in both symptoms and quality of life (QOL). 5 However, local complications such as synechiae formation, middle turbinate lateralization, and mucosal edema can impede postoperative healing and ultimately compromise long-term surgical outcomes. 6,7 In their systematic review, Hobson and colleagues evaluate the utility of middle meatal packing in reducing the risk of scarring following ESS. 8 A meta-analysis of pooled data from eighteen randomized controlled trials was performed, which demonstrated a nonsignificant trend toward decreased adhesions in patients in whom middle meatal packing was placed. 8 Like ESS, endonasal endoscopic skull base surgery (EESBS) can also lead...

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The Blood-Brain Barrier and Nasal Drug Delivery to the Central Nervous System

Abstract: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Cited by 83 publications

References 67 publications

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease

Editorial: New Perspectives in the Pathogenesis and Management of Rhinologic and Allergic Airway Disease

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The Blood-Brain Barrier and Nasal Drug Delivery to the Central Nervous System

Abstract: Despite extensive efforts to develop new techniques to cross the BBB, none has proved sufficiently effective in reaching the brain, whereas minimizing adverse effects and the endoscopic mucosal grafting technique offers new potential promise.

Cited by 83 publications

References 67 publications

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception

Nanotechnology-based drug delivery systems for the treatment of Alzheimer&rsquo;s disease

Editorial: New Perspectives in the Pathogenesis and Management of Rhinologic and Allergic Airway Disease

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Product

Resources

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Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease