Effect of flow lamination device on aerosolized drug delivery characteristics

呼吸道是最具吸引力的雾化药物输送途径之一 对肺部和全身循环的影响。它是最快的，它没有药物外流转运体和代谢 它有巨大的肺泡表面积(700平方英尺)，在肺泡水平有非常薄的粘膜屏障。 (0.1 mm)，与任何其他器官或系统不同，它由100%的心输出量灌流。然而，有一些 有效地向下肺输送和利用大的肺泡面面临严峻的挑战 区域。高达80%的药物可能储存在上呼吸道，其中大部分储存在口咽区， 造成副作用和浪费，并使交付到目标区域不可预测、效率低下，甚至 不可靠。因此，克服上呼吸道障碍，如口咽，对于提高效率很重要。 将药物输送到下肺。在这一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尤为重要。以及一个可以产生影响的单一因素 其中三个都是气溶胶输送装置出口的湍流，这一点还没有被研究过。 足以作为一个独立的因素。 在我们之前的研究中，ModiFlow已经被证明可以减少来流中的湍流，并改善 向远距离目标输送气雾剂的效率。这项拟议研究的目标是测试 ModiFlow用于改善雾化药物跨越口咽部空间障碍的输送。 目的1：测试ModiFlow分层流改善雾化吸入的能力 氟替卡松到3D黏膜组织模型，放置在屏障仿制中。 目标2：操纵ModiFlow几何形状以获得最佳出口处的气溶胶流动特性 障碍模仿者。 屏障模拟是为了模仿呼吸道中口咽屏障的两个主要特征 --收窄和弯曲。通过策略性地将3D粘膜组织模型放置在狭窄处和 弯曲的末端，通过测量它们上的药物沉积，我们将能够得出关于 流动分层对克服这些类型的障碍的影响。同时，详细地刻画了 从障碍物远端流出的气溶胶的模拟将对ModiFlow几何形状的影响倾泻光芒 为改善这些效果提供了有价值的信息。 建议的研究结果将有助于更好地了解设备外流中湍流的影响。 关于通过上呼吸道屏障向下肺输送气雾剂的效率。

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.