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

作者诚挚地感谢过敏和传染病研究所的资金来进行这项研究。

1.充填机的组件的制备<ol><li>通过钻孔或通过简单地研磨或切断底部用砂轮或锋利的剪刀穿孔0.5mL的聚丙烯微量离心管的底部。确保该孔是在中心和是不超过2毫米，直径不小于1毫米的直径（ 图1）。 </li><li>穿孔的离心管的顶部。使用＃22的钻头（约4毫米直径），在帽的中心钻一个孔。这导致，将适合的滑动尖端注射器（ 图1）的孔。 </li><li>准备细筛将被插入到离心管。?...

<ol>
	<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>

从充填机将分散体适用于动物，其接收通过被动鼻式呼吸治疗剂量，表明分散成基本颗粒大小的气溶胶的相当大的比例。这些充填机可用于气管内给药， 在粉末性能体外评价，和通用干粉气雾剂的分散以供分析或有效的实验。如果用于肺内递送，它以使用空气的供选择的种类适当体积，如过度膨胀的肺部可引起组织损伤和歪曲药代动力学结果是重要的。 5毫升的量已在豚鼠中已经使?...

<html>新的治疗产品的开发需要在动物模型中的功效测试。管理的肺途径可用于局部和系统1输送药物。干粉气雾剂的评价必要的有效分散机构，以保持在一个曝光室或用于直接施用气管内高浓度。尽管存在解决方案通过被动吸入暴露动物的干粉气雾剂，最需要的粉末群众大过量输送2的剂量。 这就排除进行早期可行性研究，药物不足，可在研究或发展初期，以支持传统的气雾剂输送系统的剂量交付要求。 当设计气雾剂药物产品，空气动力学性能可以直接涉及递送效率和功效&gt; 3。粉末成气雾剂的分散需要能量输入足以克服颗粒间力，并且颗粒工程方法可以显着提高性能气雾剂4，5，6。我们已经开发出一种分散系统（计量器），它可以有效地雾化工程化干粉气雾剂用于直接肺吹入，分散体的目的为曝光系统或生成用于分析目的。

<table border="0" cellpadding="0" cellspacing="0" width="1158">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="21">
			<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>
		<tr height="21">
			<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>
		</tr>
	</tbody>
</table>

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.

用于容易地分散的粉剂如喷雾干燥的，意图用于肺部递送5，8，9，所述充填机输送bolus剂量离开装置。有许多应用程序的充填机，包括体外颗粒表征，在活的动物直接肺内施用，和被动吸入气雾剂系统发电。 为了证明从充填机粉末分散体的效率，先?...

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

在药物对肺部给药的发展，有必要在动物模型来评价药代动力学和药效。我们呈现给从可以用于施用肺内干粉气雾剂到啮齿动物的现成组件构建的一次性气雾剂分散系统的方法。

一次性充填机对治疗药物的肺吹入小动物

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

支气管Thermoplasty：严重哮喘的一种新的治疗方法

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

科研

医学

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

原位Xenografting人类荧光素酶标记的恶性外周神经鞘瘤细胞在体内测试候选治疗药物

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

交付的治疗药物通过侧脑室（ICV）和静脉（IV）注射液在小鼠

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

持续时间较长的小鼠全身热疗协议

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

电脑断层导引的时域漫荧光体层摄影术在小动物的肿瘤生物标志物的本土化

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

肺气肿，小气道重塑的香烟烟雾暴露小鼠自动测量

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基因沉默：一个七聚物型小导RNA库的筛选潜在的癌症治疗药

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

一种优化的埃文斯蓝协议对小鼠血管泄漏的评估

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

一种从成年大鼠肾脏中分离完整型肾小球的有效筛分方法

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

经过验证的LC-MS/MS面板，用于在小头发样本中量化11种耐药结核病药物

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