Name: disposable dosators for pulmonary insufflation of therapeutic agents to small animals
Uploaded: 2017-03-30T13:00:00
Description: Watch this Scientific Journal Video about Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals at JoVE.com

著者は、この研究を行うための資金調達のためのアレルギーのための国立研究所感染症を親切に感謝したいと思います。

Dosatorsの成分の調製<ol><li>穿孔によって、または単に粉砕または研削砥石またははさみの鋭い一対の底部を切断することによって0.5mLのポリプロピレン製マイクロ遠心管の底部を穿孔。穴が中心にあり、直径はこれ以上2mm以下、直径ない1mm未満（ 図1）であることを確認してください。 </li><li>マイクロチューブの上部を穿孔。 ＃22ドリルビット（直径約4mm）を使用して、キャッ?...

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	<li>Young, E. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+Pyrazinoic+Acid+Esters+for+the+Treatment+of+Tuberculosis.">Inhaled Pyrazinoic Acid Esters for the Treatment of Tuberculosis.</a> Pharmaceutical Research. , 1-11 (2016).</li><li>Hinds, W. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Aerosol Technology: Properties, Behavior, and Measurement of Airborne Particles. , (2012).</li><li>Islam, N., Gladki, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+inhalers+(DPIs)-A+review+of+device+reliability+and+innovation.">Dry powder inhalers (DPIs)-A review of device reliability and innovation.</a> International Journal of Pharmaceutics. 360 (1-2), 1-11 (2008).</li><li>Chan, H. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+aerosol+delivery+systems:+current+and+future+research+directions.">Dry powder aerosol delivery systems: current and future research directions.</a> J Aerosol Med. 19 (1), 21-27 (2006).</li><li>Vehring, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pharmaceutical+Particle+Engineering+via+Spray+Drying.">Pharmaceutical Particle Engineering via Spray Drying.</a> Pharmaceutical Research. 25 (5), 999-1022 (2008).</li><li>Bosquillon, C., Lombry, C., Pr&#233;at, V., Vanbever, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Influence+of+formulation+excipients+and+physical+characteristics+of+inhalation+dry+powders+on+their+aerosolization+performance.">Influence of formulation excipients and physical characteristics of inhalation dry powders on their aerosolization performance.</a> Journal of Controlled Release. 70 (3), 329-339 (2001).</li><li>Hickey, A. J., Concessio, N. M., Van Oort, M. M., Platz, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+influencing+the+dispersion+of+dry+powders+as+aerosols.">Factors influencing the dispersion of dry powders as aerosols.</a> Pharmaceutical Technology. 18 (8), 58-64 (1994).</li><li>Garcia-Contreras, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Inhaled+large+porous+particles+of+capreomycin+for+treatment+of+tuberculosis+in+a+guinea+pig+model.">Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.</a> Antimicrob Agents Chemother. 51 (8), 2830-2836 (2007).</li><li>Durham, P. G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spray+Dried+Aerosol+Particles+of+Pyrazinoic+Acid+Salts+for+Tuberculosis+Therapy.">Spray Dried Aerosol Particles of Pyrazinoic Acid Salts for Tuberculosis Therapy.</a> Molecular Pharmaceutics. 12 (8), 2574-2581 (2015).</li><li>Sung, J. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry+powder+nitroimidazopyran+antibiotic+PA-824+aerosol+for+inhalation.">Dry powder nitroimidazopyran antibiotic PA-824 aerosol for inhalation.</a> Antimicrob Agents Chemother. 53 (4), 1338-1343 (2009).</li><li>Guillon, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pulmonary+delivery+of+dry+powders+to+rats:+tolerability+limits+of+an+intra-tracheal+administration+model.">Pulmonary delivery of dry powders to rats: tolerability limits of an intra-tracheal administration model.</a> Int J Pharm. 434 (1-2), 481-487 (2012).</li><li>Morello, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dry-powder+pulmonary+insufflation+in+the+mouse+for+application+to+vaccine+or+drug+studies.">Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies.</a> Tuberculosis. 89 (5), 371-377 (2009).</li></ol>

動物は、一次粒子サイズに分散したエアロゾルの大部分を示し、受動鼻のみの呼吸を介し​​て治療用量を受けるようにするためdosatorsから分散液が好適でした。これらのdosatorsは、分析や効果的な実験のために体外粉末性能の評価、および汎用乾燥粉末エアロゾル分散に 、気管内投与のために使用することができます。肺内送達のために使用された場合、組織の損傷を引き起?...

<html>新しい治療薬の開発は、動物モデルでの有効性試験が必要です。投与の肺経路は、局所的および全身1薬物を送達するために利用することができます。乾燥粉末エアロゾルの評価は、露光チャンバ内にまたは直接気管内投与のために高い濃度を維持するための効率的な分散メカニズムを必要とします。溶液は、粉末エアロゾルを乾燥する受動吸入により動物を露出させるために存在するが、ほとんどが2送達用量の大過剰の粉末の質量を必要とします。 不十分な薬剤は、従来のエアロゾル送達システムのための用量送達の要件をサポートするための研究や開発初期段階で入手できますので、これは初期のフィージビリティスタディを実施不可能にします。 エアゾール製剤を設計する際に、空気力学的性能は、送達効率および有効性に直接関係することができ&gt; 3。エアロゾル化粉末の分散は、粒子間力を克服するのに十分なエネルギー入力を必要とし、粒子工学的アプローチは、実質的にエアロゾル性能4、5、6を向上させることができます。我々は、直接肺吹送、分析目的のために、露光システムまたは生成への分散のために効率的に操作された乾燥粉末エアロゾルをエアロゾル化することができる分散系（dosator）を開発しました。

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			<td height="21" style="height:21px;width:695px;">0.5 mL microcentrifuge tube</td>
			<td style="width:139px;">VWR</td>
			<td style="width:119px;">89000-026</td>
			<td style="width:207px;"></td>
		</tr>
		<tr height="23">
			<td height="23" style="height:23px;">High-Volume Particle-Filtering Stainless Steel Wire Cloth, Woven, 304 Stainless Steel, 60 x 60 Mesh, .0045&#34; Wire Diameter</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">9230T44</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;">Stainless Steel Dispensing Needle, Straight, 18 Gauge, 1&#34; Long</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">75165A676</td>
			<td>Any luer-fit needle will suffice</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:695px;">Cotton balls</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">54845T16</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:695px;">Parafilm M&#174; Laboratory Film</td>
			<td style="width:139px;">VWR</td>
			<td>100229-550</td>
			<td></td>
		</tr>
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			<td height="21" style="height:21px;">Black-Oxide High-Speed Steel Jobbers&#39; Drill Bit, Wire Gauge 22, 3-1/8&#34; Overall Length, 1.8&#34; Drill Depth, 135Deg Point</td>
			<td style="width:139px;">McMaster Carr</td>
			<td style="width:119px;">2901A195</td>
			<td></td>
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disposable dosators for pulmonary insufflation of therapeutic agents to small animals

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver drugs locally and systemically. Evaluation of dry powder aerosols necessitates an efficient dispersion mechanism to maintain high concentrations in an exposure chamber or for direct endotracheal administration. While solutions exist to expose animals by passive inhalation to dry powder aerosols, most require masses of powder in large excess of the dose delivered. This precludes conducting early feasibility studies as insufficient drug is available at the research or early development stage to support the dose delivery requirements for conventional aerosol delivery systems. When designing an aerosol drug product, aerodynamic performance can relate directly to delivery efficiency and efficacy. Dispersion of powder into an aerosol requires energy input sufficient to overcome interparticulate forces, and particle engineering approaches can substantially improve aerosol performance. We have developed a dispersion system (dosator) which can aerosolize engineered dry powder aerosols efficiently for the purpose of direct pulmonary insufflation, dispersion into an exposure system or generation for analytical purposes.

などの容易分散性粉末のために噴霧乾燥された肺送達5、8、9のための意図では、dosatorsがデバイスの外ボーラス用量を送達するものです。受動的な吸入システムのための試験管内粒子特性評価、生きた動物での直接肺内の管理、およびエアロゾルの生成に含めdosatorsのための多くのア?...

Watch this Scientific Journal Video about Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals at JoVE.com

Disposable Dosators for Pulmonary Insufflation of Therapeutic Agents to Small Animals

肺送達のための医薬品の開発中には、動物モデルにおける薬物動態及び有効性を評価する必要があります。我々は、齧歯類に肺内乾燥粉末エアロゾルを投与するために使用することができる市販の成分から使い捨てエアロゾル分散システムを構築する方法を提示します。

小動物への治療薬の肺内吸入のための使い捨てDosators

Development of new therapeutic products requires efficacy testing in an animal model. The pulmonary route of administration can be utilized to deliver ...

Research

JoVE Journal

Medicine

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

気管支熱形成術：重篤な喘息の新しい治療アプローチ

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

Orthotopic Xenografting of Human Luciferase-Tagged Malignant Peripheral Nerve Sheath Tumor Cells for in vivo Testing of Candidate Therapeutic Agents

Orthotopic Xenografting of Human Luciferase-Tagged Malignant Peripheral Nerve Sheath Tumor Cells for in vivo Testing of Candidate Therapeutic Agents

のために人間のルシフェラーゼ-タグ付き悪性末梢神経鞘腫瘍細胞の同所Xenografting in vivoで</em候補治療薬の>テスト

Although in vitro screens are essential for the initial identification of candidate therapeutic agents, a rigorous assessment of the drug's ability to ...

Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice

Delivery of Therapeutic Agents Through Intracerebroventricular ICV and Intravenous IV Injection in Mice

マウスの脳室内（ICV）と静脈（IV）注入による治療薬のデリバリー

Despite the protective role that blood brain barrier plays in shielding the brain, it limits the access to the central nervous system (CNS) which most ...

Protocol for Long Duration Whole Body Hyperthermia in Mice

マウスの長い持続時間の全身温熱療法のためのプロトコル

Hyperthermia is a general term used to define the increase in core body temperature above normal. It is often used to describe the increased core body ...

Computed Tomography-guided Time-domain Diffuse Fluorescence Tomography in Small Animals for Localization of Cancer Biomarkers

癌バイオマーカーの局在の小型動物のCTガイド下時間領域拡散蛍光トモグラフィー

Small animal fluorescence molecular imaging (FMI) can be a powerful tool for preclinical drug discovery and development studies1. However, light ...

Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice

肺気腫とタバコ煙曝露マウスにおける末梢気道リモデリングの自動測定

COPD is projected to be the third most common cause of mortality world-wide by 2020(1).  Animal models of COPD are used to identify molecules that ...

TRUE Gene Silencing: Screening of a Heptamer-type Small Guide RNA Library for Potential Cancer Therapeutic Agents

TRUE遺伝子サイレンシング：潜在的ながん治療薬の七量体型スモールガイドRNAライブラリーのスクリーニング

TRUE gene silencing (termed after tRNase ZL-utilizing efficacious gene silencing) is one of the RNA-directed gene silencing technologies, which utilizes ...

An Optimized Evans Blue Protocol to Assess Vascular Leak in the Mouse

最適化されたエバンス ブルー マウス血管漏出を評価するためにプロトコル

Vascular leak, or plasma extravasation, has a number of causes, and may be a serious consequence or symptom of an inflammatory response. This study may ...

An Efficient Sieving Method to Isolate Intact Glomeruli from Adult Rat Kidney

ラット腎臓からそのまま糸球体を分離する効率的なふるい分け法

Preservation of glomerular structure and function is pivotal in the prevention of glomerulonephritis, a category of kidney disease characterized by ...

Validated LC-MS/MS Panel for Quantifying 11 Drug-Resistant TB Medications in Small Hair Samples

小さな毛髪サンプルで11の薬剤耐性結核薬を定量化するための検証済みのLC-MS/MSパネル

Drug resistant-tuberculosis (DR-TB) is a growing public health threat, and assessment of therapeutic drug levels may have important clinical benefits. ...