Nasal Mucociliary Clearance affecting local Drug-absorption in Subject-specific Geometries

项目摘要 药物给药通常是通过摄入过程或通过侵入性程序。 有一种通过鼻腔输送药物的有效方法。直接给药的鼻腔途径- 气雾剂递送是对抗各种病理状况的有吸引力的方法。例如，如果快速 可以确保递送的药物通过粘液层在鼻上皮吸收， 该方法能够快速起效，避免制剂在消化系统中分解， 通过新陈代谢和副作用。为了模拟和分析吸入药物气溶胶在鼻腔中的转归， 腔，包括溶解和吸收的粘液层，一个验证和全面的计算机 仿真模型是一种非常有用和具有成本效益的工具。 因此，根据当前的研究活动和FDA的资助机会，具体目标是： (i)瞬时三维粘膜纤毛清除率（MCC）和相互作用颗粒的开发和验证 运输/沉积模型应用于不同的鼻腔几何形状。 (ii)使用代表性配置模拟和分析药物-气溶胶传输、沉积 吸收和清除;所有这些都受到不同入口条件的影响， 几何学 (iii)撰写研究论文以及完成OpenFOAM用户手册。 这些研究目标可以通过开发和测试所提出的计算流体来实现- 开源软件（即OpenFOAM）中的粒子动力学模型。通过新的易于使用的数字 模拟不同的几何鼻子到气管配置，解决受试者的可变性，空气颗粒， 影响药物-气溶胶转运/沉积的粘液相互作用，以及粘液纤毛清除（MCC）， 将模拟不同鼻腔入口条件的药物转运和吸收动力学， 分析了

Project Summary Drug administering has conventionally been through the process of ingestion or via invasive procedures. There is an efficient way of delivering drugs through the nasal cavity. The nasal route for direct drug- aerosol delivery is an attractive approach to combat various pathological conditions. For example, if rapid absorption of the delivered drugs can be ensured at the nasal epithelium through the mucus layer, this methodology enables fast onset of action avoiding formulation breakdown in the digestive system and first- pass metabolism and side effects. In order to simulate and analyze the fate of inhaled drug-aerosols in nasal cavities, including dissolution and absorption in the mucus layer, a validated and comprehensive computer simulation model is a very useful and cost-effective tool. Hence, based on the current research activities and the FDA funding opportunity, the specific aims are: (i) Development and validation of transient 3-D mucociliary clearance (MCC) and interactive particle transport/deposition models applied to different nasal geometries. (ii) Use of a representative configuration to simulate and analyze drug-aerosol transport, deposition, absorption and clearance; all subject to different inlet conditions and possibly obstructed nasal geometries. (iii) Writing of research papers as well as completion of a user’s manual in OpenFOAM. These research objectives can be achieved by developing and testing the proposed computational fluid- particle dynamics model in open-source software (ie, OpenFOAM). With the new easy-to-use numerical model different geometric nose-to-trachea configurations addressing subject-variability, air-particle- mucus interactions affecting drug-aerosol transport/deposition, and mucociliary clearance (MCC) with drug transport and absorption dynamics for different nasal inlet conditions will be simulated and analyzed.