用于人体呼吸道药物沉积效力分析的离散相和欧拉壁膜耦合模型

IF 4.5 2区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Molecular Pharmaceutics Pub Date : 2024-10-07 Epub Date: 2024-09-23 DOI:10.1021/acs.molpharmaceut.4c00482
Sameer Kumar Verma, Kishore Singh Patel, B Kiran Naik
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引用次数: 0

摘要

目前的研究探讨了药物微粒沉积到人体呼吸道中治疗各种肺部疾病的有效性。假定药物溶液以微小液滴或雾状形式被吸入,撞击后沿呼吸道内表面形成薄层,病毒最初在此停留并感染人体。基于欧拉壁膜(EWF)和离散相模型(DPM)的耦合模拟方法可用于捕捉这些动态变化。在这里,拉格朗日 DPM 技术跟踪微小液滴的动态,而撞击后液层的形成则通过欧拉薄膜近似或 EWF 模型来捕捉。该领域以往的研究主要采用 DPM 方法,这种方法不足以预测撞击后药物层沉积及其扩散以中和呼吸道病毒的动态。在 15、30 和 60 升/分钟(LPM)的吸入速率下,药物输送效果以 1、5 和 10 μm 三种不同粒径为特征。研究发现,药物颗粒的大小对给药效果有很大影响。薄膜厚度随颗粒大小和吸入速率的增加而单调增加。不过,与第 4 代(G4)的 1 至 5 μm(≈10%)液滴大小相比,平均薄膜厚度在 5 至 10 μm(≈60%)范围内的增加非常明显。其他沉积参数(如沉积分数、沉积密度和面积覆盖率)随着液滴尺寸的增加大致呈现出类似的行为。因此,建议在 5 至 10 μm 之间改变液滴大小,以获得更好的沉积效果。大于 10 μm 的液滴大多会进入口腔,无法到达目标世代。相反,小于 5 μm 的微滴可以到达比目标代更深的地方。
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Coupled Discrete Phase and Eulerian Wall Film Models for Drug Deposition Efficacy Analysis in Human Respiratory Airways.

The current study explores the effectiveness of drug particle deposition into human respiratory airways to cure various pulmonary-bound ailments. It has been assumed that drug solutions are inhaled in the form of tiny droplets or mist, which after striking create a thin layer along the inner surface of airways where the virus initially resides to infect the human body. A coupled Eulerian wall film (EWF) and discrete phase model (DPM) based simulation approach is used to capture these dynamics. Here, the Lagrangian DPM technique tracks the dynamics of tiny droplets, while the liquid layer formation after striking is captured using the Eulerian thin film approximations or the EWF model. Previous studies in this field primarily employed only the DPM method, which is inadequate to predict the poststriking dynamics of drug layer deposition and their spread to neutralize the respiratory virus. The drug delivery effectiveness is characterized by three different particle sizes, 1, 5, and 10 μm at the inhalation rates of 15, 30, and 60 L per minute (LPM). It has been found that the size of the drug particles significantly influences drug delivery effectiveness. The film thickness increases monotonically with particle sizes and inhalation rates. However, this increase in averaged film thickness is prominent in the range 5 to 10 μm (≈60%) compared to 1 to 5 μm (≈10%) droplet sizes at generation level 4 (G4). The other deposition parameters, e.g., deposition fraction, deposition density, and area coverage) roughly show similar behavior with the increase in droplet sizes. Therefore, it is recommended to vary the droplet sizes between 5 and 10 μm for better deposition effectiveness. The sizes of more than 10 μm mostly stuck into the oral cavity and cannot reach the targeted generations. In contrast, less than 5 μm may reach much deeper generations than the targeted one.

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来源期刊
Molecular Pharmaceutics
Molecular Pharmaceutics 医学-药学
CiteScore
8.00
自引率
6.10%
发文量
391
审稿时长
2 months
期刊介绍: Molecular Pharmaceutics publishes the results of original research that contributes significantly to the molecular mechanistic understanding of drug delivery and drug delivery systems. The journal encourages contributions describing research at the interface of drug discovery and drug development. Scientific areas within the scope of the journal include physical and pharmaceutical chemistry, biochemistry and biophysics, molecular and cellular biology, and polymer and materials science as they relate to drug and drug delivery system efficacy. Mechanistic Drug Delivery and Drug Targeting research on modulating activity and efficacy of a drug or drug product is within the scope of Molecular Pharmaceutics. Theoretical and experimental peer-reviewed research articles, communications, reviews, and perspectives are welcomed.
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