Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review.
TL;DR: The prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines, so the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored.
Abstract: Nasal delivery is the logical choice for topical treatment of local diseases in the nose and paranasal sinuses such as allergic and non-allergic rhinitis and sinusitis. The nose is also considered an attractive route for needle-free vaccination and for systemic drug delivery, especially when rapid absorption and effect are desired. In addition, nasal delivery may help address issues related to poor bioavailability, slow absorption, drug degradation, and adverse events in the gastrointestinal tract and avoids the first-pass metabolism in the liver. However, when considering nasal delivery devices and mechanisms, it is important to keep in mind that the prime purpose of the nasal airway is to protect the delicate lungs from hazardous exposures, not to serve as a delivery route for drugs and vaccines. The narrow nasal valve and the complex convoluted nasal geometry with its dynamic cyclic physiological changes provide efficient filtration and conditioning of the inspired air, enhance olfaction, and optimize gas exchange and fluid retention during exhalation. However, the potential hurdles these functional features impose on efficient nasal drug delivery are often ignored. With this background, the advantages and limitations of existing and emerging nasal delivery devices and dispersion technologies are reviewed with focus on their clinical performance. The role and limitations of the in vitro testing in the FDA guidance for nasal spray pumps and pressurized aerosols (pressurized metered-dose inhalers) with local action are discussed. Moreover, the predictive value and clinical utility of nasal cast studies and computer simulations of nasal airflow and deposition with computer fluid dynamics software are briefly discussed. New and emerging delivery technologies and devices with emphasis on Bi-Directional™ delivery, a novel concept for nasal delivery that can be adapted to a variety of dispersion technologies, are described in more depth.
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TL;DR: This review presents some possibilities to enhance the drug penetration through the nasal barrier and summarizes some in vitro, ex vivo and in vivo technologies to test the drug delivery across the nasal epithelium into the brain.
393 citations
Cites methods from "Nasal drug delivery devices: charac..."
...(a) a traditional liquid spray, (b) the breath-powered Bi-DirectionalTM powder device, and (c) the breath-powered Bi-DirectionalTM liquid spray device (Djupesland, 2013; Djupesland and Skretting, 2012)....
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TL;DR: The benefit of the incorporation of mucoadhesive polymers into the structure of these innovative pharmaceutical products to prolong their residence time in the administration site and the release of the drug cargo will be discussed with focus in the developments of the last decade.
388 citations
TL;DR: It is demonstrated in vivo that naïve Mϕ exosomes, after intravenous (IV) administration, cross the blood-brain barrier and deliver a cargo protein, the brain derived neurotrophic factor (BDNF), to the brain.
354 citations
Cites background from "Nasal drug delivery devices: charac..."
...Furthermore, this administration route has high variability in the do se reaching the brain due to variability in drug disposition and is limited by the drug amounts that can be delivered in humans [4]....
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TL;DR: This review aims to describe the latest development of brain targeted DDSs via nasal administration that directly delivers the drugs to brain without systemic absorption, thus avoiding the side effects and enhancing the efficacy of neurotherapeutics.
233 citations
Cites background from "Nasal drug delivery devices: charac..."
...Bi-Directional Breath Powered drug delivery technology exploits the normal breath process of the body to deposit the drug on nasal epithelium [270]....
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TL;DR: Outcomes of this analysis indicate that efficiency of brain delivery by the nasal route differs widely between the studies, and does not correlate with the drug's physicochemical properties.
227 citations
Cites background from "Nasal drug delivery devices: charac..."
..., the species of the animal, disease state), administration technique [15], etc....
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References
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TL;DR: These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD.
Abstract: Objective To examine the effects of intranasal insulin administration on cognition, function, cerebral glucose metabolism, and cerebrospinal fluid biomarkers in adults with amnestic mild cognitive impairment or Alzheimer disease (AD). Design Randomized, double-blind, placebo-controlled trial. Setting Clinical research unit of a Veterans Affairs medical center. Participants The intent-to-treat sample consisted of 104 adults with amnestic mild cognitive impairment (n = 64) or mild to moderate AD (n = 40). Intervention Participants received placebo (n = 30), 20 IU of insulin (n = 36), or 40 IU of insulin (n = 38) for 4 months, administered with a nasal drug delivery device (Kurve Technology, Bothell, Washington). Main Outcome Measures Primary measures consisted of delayed story recall score and the Dementia Severity Rating Scale score, and secondary measures included the Alzheimer Disease's Assessment Scale–cognitive subscale (ADAS-cog) score and the Alzheimer's Disease Cooperative Study–activities of daily living (ADCS-ADL) scale. A subset of participants underwent lumbar puncture (n = 23) and positron emission tomography with fludeoxyglucose F 18 (n = 40) before and after treatment. Results Outcome measures were analyzed using repeated-measures analysis of covariance. Treatment with 20 IU of insulin improved delayed memory (P Conclusions These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. Trial Registration clinicaltrials.gov Identifier: NCT00438568
1,047 citations
TL;DR: This review focuses on the current understanding of the mechanisms underlying intranasal delivery to the central nervous system involving the olfactory and trigeminal nerves, the vasculature, the cerebrospinal fluid, and the lymphatic system.
968 citations
"Nasal drug delivery devices: charac..." refers background in this paper
...In the context of nasal drug delivery, perivascular spaces along the olfactory and trigeminal nerves acting as lymphatic pathways between the CNS and the nose have been implicated in the transport of molecules from the nasal cavity to the CNS [34]....
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TL;DR: The problems associated with nasal drug delivery and how it is possible, sometimes by means of quite simple concepts, to improve transport across the nasal membrane to deliver efficiently challenging drugs such as small polar molecules, peptides and proteins.
965 citations
"Nasal drug delivery devices: charac..." refers background in this paper
...For some liquid formulations, in particular peptides and proteins, limited stability of dissolved drug may represent a challenge [46]....
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TL;DR: An evaluation of the risks and benefits indicates that live attenuated vaccine should be a highly effective, safe vaccine for children 12 to 59 months of age who do not have a history of asthma or wheezing.
Abstract: BACKGROUND: Universal vaccination of children 6 to 59 months of age with trivalent inactivated influenza vaccine has recently been recommended by U.S. advisory bodies. To evaluate alternative vacci ...
771 citations
TL;DR: This study suggests a strong association between the inactivated intranasal influenza vaccine used in Switzerland and Bell's palsy.
Abstract: Background After the introduction of an inactivated intranasal influenza vaccine that was used only in Switzerland, 46 cases of Bell's palsy were reported. Methods We conducted a matched case–control study and a case-series analysis. All primary care physicians, ear, nose, and throat specialists, and neurologists in German-speaking regions of Switzerland were requested to identify cases of Bell's palsy diagnosed in adults between October 1, 2000, and April 30, 2001. Each physician was invited to select three control patients for each patient with Bell's palsy, with matching according to age, date of the clinic visit, and physician. Vaccination information was provided by the physicians. Results A total of 773 patients with Bell's palsy were identified. Of the 412 (53.3 percent) who could be evaluated, 250 (60.7 percent) were enrolled and matched with 722 control patients; the other 162 patients had no controls. In the case–control study, we found that 68 patients with Bell's palsy (27.2 percent) and 8 con...
763 citations