Nanoparticle clearance from the airways : development and testing of a new in vitro model to investigate mucociliary clearance of aerosol particles

摘要

The current challenge in pulmonary drug delivery is to overcome and to control drug clearance from the lung. Here, the interaction with the mucociliary lung clearance plays a key role for any drug formulation technology. By today many open questions on mucociliary clearance (MC) have to be answered but suffer from limited experimental options. Considering these facts, the central part of this work was to develop a new in vitro test model to investigate the complex mechanism of MC more detailed. In a next step the new model was employed to study the influence of different factors on mucociliary particle clearance. From the overall results it can be concluded that: 1) A new embryonic chicken trachea-based in vitro model to study MC was successfully developed and characterized. 2) The model exhibits a stability and sensitivity for environmental as well as chemical influences reflecting the in vivo situation. 3) Size and ζ-potential (ZP) seem to be minor critical factors for mucociliary particle clearance, which could be shown for different polymeric particles covering a broad size and ZP range. 4) The chemical surface structure of nanoparticles was found to be a most relevant factor for MC, offering promising possibilities to achieve faster or slower particle transport. In summary, this model may help to clarify open questions on lung clearance, strongly limiting the benefit of pulmonary drug delivery, and to realize the u273Ru27; concept in animal testing: Reduce, Refine, and Replace.