In Vitro Pharmacokinetics and Dosimetry
Dosimetry and pharmacokinetics of nanomaterials is essential for the design and interpretation of in vitro toxicity/biocompatibility studies. (Full size image)
Comparison of idealized dose response data demonstrating that using nominal media mass (B) concentrations obscures underlying dose-response patterns(A). (Full size image)
Dosimetry and pharmacokinetics of nanomaterials is essential for the design and interpretation of in vitro toxicity/biocompatibility studies. Response data collected in vitro can be compared across particle types and sizes and extrapolated to in vivo exposures for hazard assessment if cellular doses, not media concentrations, are used. We have developed experimental methods for directly measuring cellular doses in vitro using confocal, bright field and electron microscopy. Delivery and cellular uptake of nanostructured materials larger then the diffraction limit of light can be directly observed using confocal microscopy or bright field microscopy. Smaller low density materials require labeling with fluorophores and use of fluorescence detectors for the same methods to work. In vitro dosimetry of metal nanomaterials with higher densities can be studied directly using new wet-cell scanning electron microscopy methods or transmission electron microscopy.
These capabilities are used in combination with a unique computational model of in vitro particokinetics and cellular dosimetry to measure or estimate delivered dose to cells in vitro. Applying the basic principles dosimetry to in vitro studies enables cross particle comparisons and extrapolation of in vitro dose-response relationships to in vivo exposures. Major applications of these capabilities include:
- Design of interpretable in vitro nanotoxicology studies
- In vitro-in vivo extrapolation of dose-response relationships
- Proper cross-particle comparison of dose-response relationships
- Design of interpretable cellular uptake studies