School of Nuclear Studies and Application, Jadavpur University, Kolkata, India.
Department of Applied Mechanics, Indian Institute of Technology Madras, Chennai, India.
PLoS Comput Biol. 2022 Jun 2;18(6):e1010143. doi: 10.1371/journal.pcbi.1010143. eCollection 2022 Jun.
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 μm. 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.
肺部药物输送系统依赖于吸入由吸入器、雾化器等气溶胶发生器产生的载药气溶胶。药物分子在沉积后会在黏液层中扩散，同时也会受到黏液纤毛输送的影响，从而将药物从初始沉积部位输送走。因此，肺部特定区域的药物可用性取决于这两种现象之间的平衡。通过气溶胶在空气中的传输以及药物分子在黏液层中的传输的耦合数学模型，对药物在肺部的沉积和保留进行了数学分析。通过计算求解数学模型，确定了将载药气溶胶输送到肺部深处的合适条件。这项研究确定了将药物输送到肺部深处的条件，这对于实现全身药物输送至关重要。还针对肺部的不同区域对不同参数对药物保留的影响进行了特征描述，这对于确定目标位置吸入药物的可用性非常重要。我们的分析证实，对于 1-5μm 大小范围内的气溶胶，药物输送效率仍然最高。此外，还观察到，与正常呼吸相比，当呼吸时间延长一倍时，沉积在肺部深处的药物量增加了两倍，这表明呼吸控制是增加药物输送到肺部深处的功效的一种手段。更高的功效也减少了所需吸入的药物量，以产生相同的健康效果，从而有助于最大限度地减少药物的副作用。
