In vivo toxicological and pharmacokinetics

This division uses both inhalation and in vivo instillation to assess the degree of injury and inflammation, as well as the pharmacokinetics of delivered nanomaterials. Certain characteristics of nanoparticles determine their toxic potential. For example, some nanoparticles are able to penetrate epithelial barriers and thus gain access to components of cells and of organs that are normally shielded from particle exposure. Another important determinant of potential nanoparticle toxicity is biopersistence — particles that rapidly dissolve and disappear are less likely to be hazardous than those that persist and accumulate in the lungs. We will assess deposition, redistribution, and clearance of radiolabeled nanomaterials with various properties to determine the role of each property in their pharmacokinetics. We will also continue to define nanomaterial exposures in terms of their potential to cause inflammatory responses, particularly those mediated by oxygen-dependent mechanisms. Finally, we can measure a variety of cardiopulmonary responses such as breathing pattern, heart rate, and systemic blood pressure.

Relevant publications:

  1. P. Demokritou, S. Gass, G. Pyrgiotakis, J. M. Cohen, W. Goldsmith, W. McKinney, D. Frazer, J. Ma, D. Schwegler-Berry, J. Brain and V. Castranova. “An in vivo and in vitro toxicological characterisation of realistic nanoscale CeO2 inhalation exposures”. Nanotoxicology 7, 1338 (2013). link
  2. G. A. Sotiriou, E. Diaz, M. S. Long, J. Godleski, J. Brain, S. E. Pratsinis and P. Demokritou. “A novel platform for pulmonary and cardiovascular toxicological characterization of inhaled engineered nanomaterials”. Nanotoxicology 6, 680-690 (2012). link
  3. P. Demokritou, R. Buechel, R. M. Molina, G. M. Deloid, J. D. Brain and S. E. Pratsinis. “Development and characterization of a Versatile Engineered Nanomaterial Generation System (VENGES) suitable for toxicological studies”. Inhalation Toxicology 22, 107-116 (2010). link