Effect of flow lamination device on aerosolized drug delivery characteristics

流动层压装置对雾化给药特性的影响

• 批准号: 10480263
• 负责人: Arevik Mosoian
• 金额: $ 25.96万
• 依托单位: SKINAXIS, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10480263
• 关键词: 3-Dimensional; Address; Aerosols; Alveolar; Area; Blood Circulation; Cardiac Output; Characteristics; Complex; Custom; Deposition; Destinations; Devices; Distal; Distant; Drug Delivery Systems; Drug Efflux; Drug Receptors; Enzymes; Generations; Geometry; Intercept; Length; Light; Lung; Measures; Modification; Mucous Membrane; Oral cavity; Oral mucous membrane structure; Organ; Oropharyngeal; Outcome; Pathway interactions; Pharmaceutical Preparations; Pharyngeal structure; Phase; Plum; Process; Publications; Pump; Reproducibility; Respiratory System; Role; Route; Structure; Structure of parenchyma of lung; Surface; System; Testing; Thinness; Time; Tissue Model; Tissues; absorption; aerosolized; compare effectiveness; design; fluticasone; foot; improved; prevent; prototype; side effect; square foot; wasting

The respiratory tract is one of the most attractive pathways for delivering aerosolized medications both to the lungs and to systemic circulation. It is the fastest, it's devoid of drug efflux transporters and metabolizing enzymes, it has a huge alveolar surface area (700 square feet) and a very thin mucosal barrier at alveolar level (0.1 mm), and it is perfused by 100% of cardiac output unlike any other organ or system. However there are serious challenges to efficient delivery to the lower lungs and to taking advantage of the large alveolar surface area. Up to 80% of the medication may be deposited in the upper airways, most of it in the oropharyngeal area, causing side effects and waste, and making the delivery to target areas unpredictable, inefficient, and even unreliable. Therefore overcoming the upper airway barriers such as oropharynx is important for more efficient drug delivery to the lower lungs. Among many factors involved in this process, Inertial Impaction, Turbulent Mixing and Interception are especially significant in upper airways. And a single factor that can have an impact on all 3 of them is the turbulence in the outflow of the aerosol delivery device, which has not been studied sufficiently as an independent factor. In our previous study ModiFlow has been shown to reduce turbulence in the incoming flow, and to improve the efficiency of aerosol delivery to distant targets. The objectives of the proposed study are to test the ability of ModiFlow to improve the delivery of aerosolized drugs across a spatial Barrier Imitation of the oropharynx. Objective 1: To test the ability of laminated flow from ModiFlow to improve the delivery of aerosolized Fluticasone to 3D mucosal tissue models placed within a Barrier Imitation. Objective 2: To manipulate the ModiFlow geometry to achieve the best aerosol flow characteristics at the exit of the Barrier Imitation. The Barrier Imitation is designed to mimic two main characteristics of the oropharyngeal barrier in the airways – narrowing and curving. By strategically placing 3D mucosal tissue models at the point of narrowing and at the end of curving, and by measuring the medication deposition on them, we'll be able to draw conclusions about the effects of flow lamination on overcoming these types of barriers. At the same time, detailed characterization of aerosol outflow from the distal end of the Barrier Imitation will pour light on the effects of ModiFlow geometry on it, providing valuable information for improving those effects. The outcomes of the proposed study will help better understand the effects of turbulence in the device outflow on the efficiency of aerosol delivery across upper airway barriers to the lower lungs.

呼吸道是将雾化药物输送到的最吸引人的途径之一 肺部和全身循环。它是最快的，没有药物外排运输蛋白和代谢 酶，它具有巨大的肺泡表面积（700平方英尺），并且在牙槽水平上非常薄的粘膜屏障 （0.1毫米），与其他任何器官或系统不同，它被100％的心输出量灌注。但是有 有效输送到下肺并利用大牙槽表面面临的严重挑战 区域。多达80％的药物可以沉积在上呼吸道中，其中大部分在口咽区域， 造成副作用和浪费，并使到目标区域的交付不可预测，效率低下，甚至 不可靠。因此，克服诸如口咽等上空气道屏障对于更有效的效率很重要 药物输送到下肺。在此过程中涉及的许多因素中，惯性撞击，湍流 混合和拦截在上呼吸道中尤其重要。以及可能产生影响的一个因素 在所有三个是气溶胶递送装置出口中的湍流，尚未研究 足够作为独立因素。 在我们先前的研究中 气溶胶递送到遥远目标的效率。拟议研究的目标是测试 Modiflow可以改善在口咽的空间屏障模仿中雾化药物的递送。 目标1：测试从Modiflow的层压流量的能力改善雾化的递送 氟替卡松（Fluticasone）到3D粘膜组织模型放置在屏障模仿中。 目标2：操纵Modiflow几何形状以达到出口处的最佳气溶胶流量特征 障碍模仿。 屏障模仿旨在模仿气道中口咽屏障的两个主要特征 - 变窄和弯曲。通过策略性地将3D粘膜组织模型放置在狭窄的点和 弯曲结束，并通过测量对它们的药物存款，我们将能够得出有关的结论 流动层压对克服这类障碍的影响。同时，详细的特征 屏障模仿远端的气溶胶出口将倒入Modiflow几何形状的影响 在上面，提供有价值的信息来改善这些效果。 拟议研究的结果将有助于更好地了解设备出口中湍流的影响 关于横跨下肺部肺部屏障的气溶胶效率。