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

项目摘要 传统上，给药是通过摄取过程或侵入性程序进行的。 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- 气雾剂释放是对抗各种病理情况的一种有吸引力的方法。例如，如果速度很快 鼻腔上皮可以通过粘液层确保药物的吸收，这 方法论能够快速起作用，避免消化系统中的配方崩溃，并首先 通过新陈代谢和副作用。为了模拟和分析吸入药物气雾剂在鼻腔内的去向 空洞，包括粘液层的溶解和吸收，一台经过验证的全面的计算机 仿真模型是一个非常有用且性价比很高的工具。 因此，根据目前的研究活动和FDA的资助机会，具体目标是： (I)瞬时3-D粘液纤毛清除(MCC)和交互粒子的开发和验证 适用于不同鼻型的传输/沉积模型。 (2)使用具有代表性的构型来模拟和分析药物-气雾剂的传输、沉积、 吸收和清除；都受到不同进气条件的影响，可能是鼻腔阻塞 几何图形。 (3)撰写研究论文以及在OpenFOAM中完成用户手册。 这些研究目标可以通过开发和测试拟议的计算流体来实现- 开源软件(如OpenFOAM)中的粒子动力学模型。使用新的易于使用的数字 模拟不同几何形状的鼻到气管配置，以解决对象可变性、空气-颗粒- 粘液相互作用影响药物-气雾剂的传输/沉积和粘液纤毛清除(MCC) 将模拟不同鼻腔进药条件下的药物传输和吸收动力学 分析过了。

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.