Influence of physicochemical properties of Nanoparticles on mucociliary and macrophage cleareance

• Antragsteller: Professor Claus-Michael Lehr, Ph.D.
• Fachliche Zuordnung: Biologische und Biomimetische Chemie
• Förderung: Förderung von 2009 bis 2011
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 87488387

Progress in powder as well as device technology allows the treatment of local and systemic diseases by inhalation aerosols. At the same time the human body possesses sophisticated clearance systems to protect the delicate air blood barrier against inhaled particles. Therefore, the interplay of the functionalized alveolar fluid layers, the macrophages, and the mucociliary clearance - as representatives of the endogenous defense mechanisms - with nanoparticles will be in the focus of this project. Working with advanced cell culture models and intelligent surface tunable nanoparticles allows to obtain fundamental insight about the influence of particle size, lipophilicity and surface charge on nanoparticle - lung interactions. By microscopic techniques the pathways of the nanoparticles across the different cellular and physical barriers will be elucidated. The interactions with the proteins in the functionalized fluid layers - especially surfactant and mucus - will be monitored by gel electrophoresis and MALDI -TOP analysis. While the interactions of nanoparticles with the epithelial barriers of the human body has been and still is intensively studied, there is a clear lack of systematic studies how inhaled nanoparticles interact with those nonepithelial barriers (i.e. mucociliary and macrophage clearance). Regarding the fact that all epithelial surfaces of the lungs are protectively covered by specialized fluid layers, the interactions of nanoparticles with mucus and surfactant are of particular importance. Advanced in-vitro models - either already available or to be further developed in our lab - combined with surface tunable intelligent particles made by our collaboration partners will allow profound investigations about the processes occurring after the first contact of inhaled nanoparticles with the human air blood barrier.

• DFG-Verfahren: Sachbeihilfen