592f Use of Physiologically Based in Vitro Models of the Gastrointestinal Tract to Study Nanoparticle Absorption and Toxicity

Gretchen J. McAuliffe1, Shivaun D. Archer2, Raymond P. Glahn3, and Michael L. Shuler2. (1) School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, (2) Department of Biomedical Engineering, Cornell University, 171 Kimball Hall, Ithaca, NY 14853, (3) Department of Food Science, Cornell University, U.S. Plant, Soil and Nutrition Laboratory, Tower Road, Ithaca, NY 14853

The field of nanotechnology offers potential for advances in areas ranging from medicine to manufacturing. As a result of this technology, there are an increasing number of nanoparticles and nanomaterials with unique physical and chemical properties that are becoming commercially available. These nanoparticles and nanomaterials present new challenges to understanding, predicting, and managing potential health risks to workers and end users. The increased surface area, unique crystalline structure, small size, and enhanced reactivity of some nanoparticles may lead to harmful interactions with cellular material, and little is known about possible adverse effects from the ingestion of nanoparticles. The goal of this research is to answer some fundamental questions about the absorption and toxicity of ingested nanoparticles using physiologically realistic in vitro models of the human gastrointestinal (GI) tract.

In vitro microscale cell culture analogs (μCCAs) are physical replicas of physiologically based pharmacokinetic models that combine microfabrication and cell culture (Biotechnol. Prog., 20 (1), 338-345, 2004). The GI tract μCCA consists of two chambers separated by a microporous membrane on which epithelial and goblet cells are cultured. Compounds of interest are subjected to an in vitro digestion then pumped through the top chamber, allowing the compound to be absorbed through the epithelial layer. Preliminary experiments with the GI tract μCCA and 50 nm, polystyrene nanoparticles have shown that 25% of the particles pass through the epithelial layer into the basolateral chamber. Epithelial and goblet cells cultured on TranswellŽ inserts transported 1.6% of the 50 nm, polystyrene nanoparticles. Iron uptake and transport was used as an indicator of normal cell function for cells grown on Transwell inserts. It was found that exposure to nanoparticles significantly altered iron transport, but not iron uptake. Cultures exposed to nanoparticles for 6 hours transported 40% more iron than control cultures not exposed to nanoparticles.