Marangoni Driven Spreading on Entangled Polymer Subphases with Application to Pulmonary Drug Delivery

马兰戈尼驱动的缠结聚合物亚相铺展及其在肺部药物输送中的应用

• 批准号: 0931057
• 负责人: Stephen Garoff
• 金额: $ 33.92万
• 依托单位: Carnegie-Mellon University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-10-01 至 2012-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0931057&HistoricalAwards=false
• 关键词: Marangoni; Driven; Spreading; Entangled; Polymer

0931057GaroffThis project will establish the fundamental wetting mechanisms required to harness surface tension gradient driven (Marangoni) flows to enhance spreading of drug delivered by aerosols in the lung. While inhaled aerosol drugs can deliver substantial doses of medication directly to the lungs, altered patterns of ventilation associated with diseased lungs cause inhaled drugs to deposit non-uniformly so that some lung regions receive very high local doses of medication while other regions go untreated. Preliminary studies suggest that the addition of surfactant to the aerosol will disperse these drugs more effectively after deposition. In the research, the PIs will identify the characteristics of surfactant formulations that optimize the efficacy of self-dispersing liquids for aerosol drug delivery. The research will build on prior research on the mechanism of spreading of exogenous fluids in the lungs of premature infants during Surfactant Replacement Therapies (SRT) but will differ in its focus in three ways. First, we focus on the final spread area of the formulation and, while not neglecting it, less on the dynamic mechanisms that lead to that final state. Second, they determine how the surfactant, the aqueous solvent, and the dissolved or solubilized surrogate drug in the droplets are distributed on the surface. Finally, the preliminary work strongly suggests a large separation in the time scales of the underlying processes in the spreading, such that the final spread droplet state is captured by a quasi-static interfacial tension balance on a flattened lens of the dosing fluid. The key to the most effective drug dispersal is to maximize the static lens area. Intellectual Merit: The discovery of effectiveness of SRT spawned considerable research into role of Marangoni flows in the airways. Theoretical analyses explored the ramifications of the complex subphases over which the transport occurs in the lungs, but experimental research focused on simpler systems. They will experimentally investigate key predictions of these analyses on rheologically complex subphases that could fundamentally alter the surfactant-driven spreading of fluids in the lung. In addition, prior work placed the emphasis on the dynamics of the initial spreading stages, but they turn the focus to the mechanisms that dictate the final disposition of the fluids, especially the dissolved or solubilized dyes that serve as model drugs. The refocusing of attention on the final state of the spread formulation represents a novel and potentially transformative approach to the problem. Broader Impacts: The results of the proposed research will guide the choice of surfactant formulations to be tested for self-dispersing carriers for aerosol drug delivery. This technology will benefit treatment of any number of obstructive lung diseases, including cystic fibrosis, asthma, pneumonia and other acute or chronic pulmonary infections. While this research focuses on fundamental physical mechanisms of enhanced drug spreading, the team collaborates with pulmonary medicine specialists in the University of Pittsburgh Medical School where our fundamental findings will guide in vivo studies. By regularly attending seminars and meetings with clinical investigators, the engineering and physics graduate students on this project will be trained in a highly interdisciplinary environment. They will mentor an undergraduate research student during each academic year and summer and at least two middle school students each year in the Carnegie Mellon/Colfax Physics Concepts Outreach Program.

0931057 Garoff该项目将建立利用表面张力梯度驱动（Marangoni）流动所需的基本润湿机制，以增强气溶胶在肺中递送的药物的扩散。虽然吸入的气雾剂药物可以将大量剂量的药物直接递送到肺，但是与患病的肺相关的通气模式的改变导致吸入的药物不均匀地存款，使得一些肺区域接收非常高的局部剂量的药物，而其他区域不进行治疗。初步研究表明，添加表面活性剂的气雾剂将更有效地分散这些药物后沉积。在研究中，PI将确定表面活性剂配方的特征，以优化自分散液体用于气雾剂药物输送的功效。该研究将建立在先前关于表面活性剂替代疗法（SRT）期间早产儿肺部外源性液体传播机制的研究基础上，但其重点将在三个方面有所不同。首先，我们专注于配方的最终扩散区域，虽然没有忽略它，但较少关注导致最终状态的动态机制。其次，它们确定液滴中的表面活性剂、水性溶剂和溶解或增溶的替代药物如何分布在表面上。最后，初步的工作强烈建议在时间尺度的基本过程中的传播，这样的最终传播液滴状态被捕获的准静态的界面张力平衡上的平坦的透镜的计量流体的大分离。最有效的药物分散的关键是最大化静态透镜面积。知识价值：SRT有效性的发现引发了对Marangoni流在气道中作用的大量研究。理论分析探索了在肺中发生运输的复杂子阶段的后果，但实验研究集中在更简单的系统上。他们将通过实验研究这些分析对流变学复杂亚相的关键预测，这些亚相可能从根本上改变肺中液体表面活性剂驱动的扩散。此外，先前的工作重点放在初始扩散阶段的动力学上，但他们将焦点转向决定流体最终处置的机制，特别是作为模型药物的溶解或增溶染料。将注意力重新集中在传播公式的最终状态上，代表了解决这个问题的一种新的和潜在的变革性方法。更广泛的影响：拟议的研究结果将指导选择表面活性剂配方进行测试的自分散载体的气雾剂给药。这项技术将有利于治疗任何数量的阻塞性肺病，包括囊性纤维化，哮喘，肺炎和其他急性或慢性肺部感染。虽然这项研究的重点是增强药物扩散的基本物理机制，但该团队与匹兹堡大学医学院的肺部医学专家合作，我们的基本发现将指导体内研究。通过定期参加研讨会和与临床研究人员的会议，该项目的工程和物理研究生将在高度跨学科的环境中接受培训。他们将在每个学年和夏季指导一名本科研究生，每年至少有两名中学生参加卡内基梅隆/科尔法克斯物理概念外展计划。