论文标题
肺部药物输送和保留:一项计算研究,旨在根据耦合气道量流模型识别合理参数
Pulmonary drug delivery and retention: a computational study to identify plausible parameters based on a coupled airway-mucus flow model
论文作者
论文摘要
肺部药物输送系统依赖于由气溶胶发电机(例如吸入器,雾化器等)产生的含有药物的气溶胶等,在沉积中,药物分子在粘液层中弥漫性,也受到粘膜胶质质量的影响,从而使药物从初始脱位位点传递出来。因此,该药物在肺的特定区域的可用性是由这两种现象之间的平衡决定的。通过气溶胶在空气中的气溶胶转运以及粘液层中的药物分子转运的数学模型开发了对肺部药物沉积和保留的数学分析。在计算上求解数学模型,以确定适合将载有药物的气溶胶运输到深肺的条件。这项研究确定了有利于将药物输送到深肺的条件,这对于实现全身药物的递送至关重要。不同参数对药物保留的影响也针对肺部的各个区域,这对于确定目标位置吸入药物的可用性很重要。我们的分析证实,在1-5 $ $ $ m的尺寸范围内的气溶胶中,药物输送功效仍然最高。此外,观察到,当呼吸时间周期翻了一番时,沉积在深肺中的药物增加了2倍,相对于正常呼吸,这表明呼吸控制是提高药物递送到深肺功效的一种手段。更高的功效还减少了吸入所需的药物负荷以产生相同的健康作用,因此可以帮助最大程度地减少药物的副作用。
Pulmonary drug delivery systems rely on inhalation of drug-laden aerosols produced from aerosol generators such as inhalers, nebulizers etc. On deposition, the drug molecules diffuse in the mucus layer and are also subjected to mucociliary advection which transports the drugs away from the initial deposition site. The availability of the drug at a particular region of the lung is, thus, determined by a balance between these two phenomena. A mathematical analysis of drug deposition and retention in the lungs is developed through a coupled mathematical model of aerosol transport in air as well as drug molecule transport in the mucus layer. The mathematical model is solved computationally to identify suitable conditions for the transport of drug-laden aerosols to the deep lungs. This study identifies the conditions conducive for delivering drugs to the deep lungs which is crucial for achieving systemic drug delivery. The effect of different parameters on drug retention is also characterized for various regions of the lungs, which is important in determining the availability of the inhaled drugs at a target location. Our analysis confirms that drug delivery efficacy remains highest for aerosols in the size range of 1-5 $μ$m. Moreover, it is observed that amount of drugs deposited in the deep lung increases by a factor of 2 when the breathing time period is doubled, with respect to normal breathing, suggesting breath control as a means to increase the efficacy of drug delivery to the deep lung. A higher efficacy also reduces the drug load required to be inhaled to produce the same health effects and hence, can help in minimizing the side effects of a drug.