Project Details
Projekt
Drug delivery to the airways – Evaluation of underlying mechanisms in a transparent airway model
Subject Area
Pneumology, Thoracic Surgery
Term
since 2017
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 394605884
The application of liquid therapeutics (solutions, suspensions or dispersions) is associated with complex transport mechanisms within the airways, depending on the application method used. These plug, film and droplet flows significantly determine the final deposition field and the maximum achievable distal penetration of liquid. At the same time, within the drug delivery system therapeutics are inevitably exposed to fluid-internal forces during transport and droplet generation, which may contribute to a decrease in the overall functionality of these substances. Both, the deposition field on the one hand and the functionality of the applied substances on the other hand, significantly determine the effectiveness of the therapeutic approach. The transparent 23-generation airway model developed in the previous project opens up new possibilities for a highly-resolved investigation of intrapulmonary transport processes. For this reason, in this continuation project, for the first time, a visualization and quantitative comparison of the fluid dynamics and deposition along the representative airway will be performed for selected application techniques. State-of-the-art jet nebulization, ultrasonic nebulization and bronchoscopic instillation will be compared with the bronchoscopic spraying method newly developed in the previous project. The investigations will be carried out for defined conditions of the drug delivery methods and different breathing patterns. Major challenges of this project are i) the validation of the airway model via combined deposition measurements on real lungs and ii) the analysis of flow phenomena on different local and temporal scales (including the long-term delivery of fine aerosol mist in the micrometer range or the short-term delivery of plugs that completely fill airways). Thus, the planned investigations require, on the one hand, complementary (laser-)optical diagnostics and, on the other hand, a specific further development of the airway model by a humidity control and a novel sampling technique. Complementary to the investigations on the airway model, the influence of the different application techniques on the functionality of distinct classes of therapeutics will be disclosed. For this purpose, the mentioned application techniques will be operated with representative enzymes and extracellular vesicles in addition to the stem cells already used in the previous project. In the long term, the investigations in this project shall contribute to more efficient, drug-sparing and targeted applications of various therapeutics into the deepest airway regions of the lung.
DFG Programme
Research Grants
