Aerosol Science and Nanoparticle Dosimetry
Dr. W. G. Kreyling (e-mail)
Overview
We are focussing on aerosol characterization, exposure assessment, and toxicokinetics of nanoparticles. It has become apparent that particle effects are evident in the lung but also adverse systemic and extra-pulmonary effects have to be considered in a comprehensive approach. This research will provide basic information for refinement of air pollution regulations as well as guidelines for safe handling of upcoming nanomaterial technologies.
Nanoparticles Dosimetry
- Uptake of particles into the body
With the rapid growth of nanotechnology, an increasing part of the population will be exposed to nanoparticulate materials. Exposure characteristics will differ during each stage of the NP life cycle from production to distribution, use and finally disposal or recycling. The primary organs of intake are the respiratory tract, the gastro-intestinal-tract and the skin. Based on our longstanding expertise in aerosol and ultrafine particle research, studies on this subtopic will concentrate on the respiratory tract and focus on inhaled nanosized particles.
- Interactions of deposited particles with lung membrane
Our recent studies show that high amounts of inhaled NP are deposited in the respiratory system and may follow routes within the organism which have not been demonstrated for micron-sized particles. Rapid translocation of inhaled NP into the lung tissue itself and, via the circulation, into secondary target organs like heart, brain or foetus could be demonstrated. We will extend these studies by applying newly developed quantitative dosimetry techniques to rodent models addressing the adult but also the developing lung and by building on recent biokinetics studies in patients with respiratory diseases at the CPC.
- First contact of deposited particles with the lung surface
Key objectives of our future studies are the quantification of regional NP deposition in the lungs, interactions of NP with lung cells, translocation and clearance of NP and assessment of accumulation doses of NP in cells, tissues and target organs of humans and animal models. Relevant NP properties of surface chemistry and physical structure will be systematically modified to predict by means of extrapolation the fate of almost any NP within the body and to provide valid dose estimates for effect-related toxicological studies (see below). We will identify particle properties associated with reduced adverse effects and low risk either for nanomedicine (see below) or general nanotechnologies.
- Transformation of aggregated insoluble particles
Current efforts in therapeutic applications of nanocarriers (NC) loaded with potent drugs aim for precise organ and cell targeting and raise questions about the fate and possible side effects of the non-drug compounds of these NC. Together with our partners in pharmacology and related to our unique research capacities on nanodosimetry and nanotoxicology we aim for the selection of superior targeting molecules and NC properties to improve specificity and sustainability of NC therapies.
