Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by fluorescence and bioluminescence

Mizuno, Tomoyuki; Mohri, Kunihiko; Nasu, Shiho; Danjo, Kazumi; Okamoto, Hirokazu

doi:10.1016/j.jconrel.2008.11.018

Cited by 53 publications

(41 citation statements)

References 33 publications

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“…133,134 Fluorescence/bioluminescence imaging systems for pulmonary gene delivery Visualization and evaluation of both the pulmonary delivery and the gene expression properties after dry powder inhalation in mice were recently reported by Mizuno and colleagues. 215 It was shown that the pulmonary delivery and Nanomedicine in pulmonary delivery Dovepress submit your manuscript | www.dovepress.com Dovepress the gene expression can be evaluated using fluorescence of indocyanine green (ICG) as a fluorescent label and the detection of luciferase activity, respectively, by using a nondestructive real-time in vivo imaging system. They concluded that the dry powder containing both ICG and pCMV-Luc was useful as a dual imaging system to visualize pulmonary delivery and gene expression in mice.…”

Section: -214mentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

394

262

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Section: -214mentioning

confidence: 99%

Nanomedicine in pulmonary delivery

Mansour¹,

Rhee²,

Wu³

2009

IJN

394

262

View full text Add to dashboard Cite

“…In our and the previous reports, dry plasmid DNA (pDNA) powders could be stably prepared by the supercritical CO 2 technique. [25][26][27][28][29] We demonstrated that a pDNA powder prepared with chitosan, a biodegradable cationic polymer, exhibited a greater pulmonary gene expressing effect and longer storage than did the solution. 26,27) These observations prompted us to use the supercritical CO 2 technique to prepare inhalable siRNA powders.…”

mentioning

confidence: 91%

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Okuda

Kito

Oiwa

et al. 2013

Biological & Pharmaceutical Bulletin

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In this study, a novel dry small interfering RNA (siRNA) powder for inhalation, containing chitosan and mannitol, was prepared using the supercritical carbon dioxide (CO 2 ) technique. Although the siRNA/chitosan powder was difficult to disperse because of a long needle-like structure, it could be reduced to fragments of 10-20 µm by manual grinding, which allowed for administration into mice. Electrophoresis revealed that the supercritical CO 2 technique and manual grinding didn't greatly affect the integrity of the siRNA. Furthermore, the siRNA was more stable in the lungs than in blood, suggesting the utility of pulmonary delivery. Biodistribution experiments using Cy5.5-labeled siRNA demonstrated that pulmonary administration of the powder achieved a prolonged exposure of the siRNA/chitosan complex on the lung epithelial surface at a higher concentration. For the evaluation of the in-vivo gene silencing effect of the siRNA/chitosan powder, mice bearing colon26/Luc cells were used. The powder significantly inhibited the increase in luminescence intensity in the lungs, but the siRNA/chitosan solution and a non-specific dry siRNA/chitosan powder didn't, indicating the effective and specific gene silencing against the tumor cells metastasized in the lungs of mice by the siRNA/chitosan powder. These results strongly indicate that inhalable dry siRNA powders have the possibility of effective pulmonary gene silencing and that the supercritical CO 2 technique can be applied to the production.Key words small interfering RNA; inhalable dry powder; supercritical fluid technique; pulmonary gene delivery; chitosan RNA interference (RNAi), first reported by Fire et al., is a unique cellular phenomenon in which double-stranded RNA (dsRNA) regulates gene expression, contributing to cellular defenses against viral infections and transposon expansion.

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“…The diameter of the particles was nearly 50 μm. Compared to the sea-urchin-like lactose particle, 23) the SS-SCF had fewer needles per particle. In general, such bulky particles are with lower density and have advantages for inhalation, because of their small aerodynamic diameter compared with their geometric diameter.…”

Section: Resultsmentioning

confidence: 93%

“…[19][20][21][22] As described previously, we successfully prepared unique sea-urchin-like lactose monohydrate particles by the supercritical carbon dioxide antisolvent (SCF) method with a V-shaped nozzle designed by us. 23) Although the sea-urchin-like lactose monohydrate particles were effective for gene delivery to the lungs in mice, their in vitro inhalation performance has not yet been investigated. We have not examined if the SCF method is applicable to other drug substances to prepare sea-urchin-like particles with high in vitro inhalation performance.…”

mentioning

confidence: 99%

Development of Dry Salbutamol Sulfate Powder with High Inhalation Performance Independent of Inhalation Patterns

Hira

Okuda

Ichihashi

et al. 2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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While dry powder inhalations are commonly used to treat pulmonary diseases, their clinical performance depends on patient inspiratory flow patterns. The purpose of this study was to develop a new powder with high and stable therapeutic performance for various patients. We applied the supercritical antisolvent (SCF) method to salbutamol sulfate (SS) to prepare a bulky SS particle (SS-SCF). Tests of in vitro inhalation performance with a human inspiratory flow simulator revealed SS-SCF to be less susceptible to inspiratory flow patterns than milled SS. When inspired, the unique structure seemed to be broken resulting in small fragments that could be delivered to the lungs. However, stability tests under physical stress showed tolerance for transportation and handling. In addition, optimization of the concentration of the SS solution applied to SCF method improved the in vitro inhalation performance of SS-SCF. These results indicated that a unique bulky SS powder prepared by the SCF method was useful for dry powder inhalation.Key words dry powder inhalation; inspiratory flow pattern; supercritical fluid drying; twin stage liquid impinger; inhalation performanceThe most common treatment for pulmonary diseases like asthma and chronic obstructive pulmonary disease (COPD) is inhalation therapy. Dry powder inhalants (DPIs) have become common in the field of inhalation therapy because they are free from environmentally damaging propellants and easy to use with small portable devices.1,2) With passive DPIs, because the aerosolization is activated by inhalation, handling is easier than that with pressurized metered dose inhalers (pMDIs). Many studies have investigated the therapeutic performance of dry powders influenced by particle size, morphology, surface roughness, crystallinity, and so on. [3][4][5] In addition, inspiratory flow patterns and inhalation devices have a significant impact on particle dispersion. [6][7][8] The clinical performance of inhalable drugs is susceptible to inspiratory patterns. 9,10) Numerous studies have shown the influence on inhalation performance of inspiratory patterns. 8,11,12) For stable therapeutic performance, not only drug administration guidance for patients but also the development of new formulations whose inhalation performance is independent of inspiratory flow patterns is needed.We previously constructed a human inspiratory flow simulator, and evaluated the influence of human inspiratory flow patterns and inhalation device type on the in vitro inhalation performance of dry salbutamol sulfate (SS) powders physically mixed with coarse lactose monohydrate powders, revealing that the effect of inspiratory flow patterns depended on the particle diameter of the active pharmaceutical ingredient (API).13) Peak flow rate (PFR) most affected in vitro inhalation performance among three critical parameters selected for the characterization of human inspiratory flow patterns; flow increase rate (FIR), inspiratory flow volume (area under the curve corresponding to inspiratory flow volume, AUC...

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Dual imaging of pulmonary delivery and gene expression of dry powder inhalant by fluorescence and bioluminescence

Cited by 53 publications

References 33 publications

Nanomedicine in pulmonary delivery

Nanomedicine in pulmonary delivery

Gene Silencing in a Mouse Lung Metastasis Model by an Inhalable Dry Small Interfering RNA Powder Prepared Using the Supercritical Carbon Dioxide Technique

Development of Dry Salbutamol Sulfate Powder with High Inhalation Performance Independent of Inhalation Patterns

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