一次性充填机对治疗药物的肺吹入小动物
Summary
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。
Abstract
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.
Introduction
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> 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。
Protocol
Representative Results
Discussion
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?…
Declarações
The authors have nothing to disclose.
Acknowledgements
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。
Materials
| 0.5 mL microcentrifuge tube | VWR | 89000-026 | |
| High-Volume Particle-Filtering Stainless Steel Wire Cloth, Woven, 304 Stainless Steel, 60 x 60 Mesh, .0045" Wire Diameter | McMaster Carr | 9230T44 | |
| Stainless Steel Dispensing Needle, Straight, 18 Gauge, 1" Long | McMaster Carr | 75165A676 | Any luer-fit needle will suffice |
| Cotton balls | McMaster Carr | 54845T16 | |
| Parafilm M® Laboratory Film | VWR | 100229-550 | |
| Black-Oxide High-Speed Steel Jobbers' Drill Bit, Wire Gauge 22, 3-1/8" Overall Length, 1.8" Drill Depth, 135Deg Point | McMaster Carr | 2901A195 |
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