Simulated Gastric Digestion and In Vivo Intestinal Uptake of Orally Administered CuO Nanoparticles and TiO<sub>2</sub> E171 in Male and Female Rat Pups
Ninell P. Mortensen,
Maria Moreno Caffaro,
Shyam Aravamudhan,
Lakshmi Beeravalli,
Sharmista Prattipati,
Rodney W. Snyder,
Scott L. Watson,
Purvi R. Patel,
Frank X. Weber,
Stephanie A. Montgomery,
Susan J. Sumner,
Timothy R. Fennell
Affiliations
Ninell P. Mortensen
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Maria Moreno Caffaro
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Shyam Aravamudhan
Joint School of Nanoscience and Nanoengineering, 2907 East Gate City Blvd., Greensboro, NC 27401, USA
Lakshmi Beeravalli
Joint School of Nanoscience and Nanoengineering, 2907 East Gate City Blvd., Greensboro, NC 27401, USA
Sharmista Prattipati
Joint School of Nanoscience and Nanoengineering, 2907 East Gate City Blvd., Greensboro, NC 27401, USA
Rodney W. Snyder
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Scott L. Watson
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Purvi R. Patel
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Frank X. Weber
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Stephanie A. Montgomery
Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Susan J. Sumner
UNC Nutrition Research Institute, The University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, USA
Timothy R. Fennell
RTI International, 3040 E Cornwallis Road, Research Triangle Park, NC 27709, USA
Oral exposure to nanoparticles (NPs) during early life is an understudied area. The goals of this study were to evaluate the effect of pre-weaned rat gastric fluids on 50 nm CuO NPs and TiO2 E171 in vitro, and to evaluate uptake in vivo. The NP uptake was studied in vivo in male and female Sprague-Dawley rat pups following oral administration of four consecutive daily doses of 10 mg/kg CuO NPs, TiO2 E171, or vehicle control (water) between postnatal day (PND) 7–10. Rat pups were sacrificed on either PND10 or PND21. Simulated digestion led to dissolution of CuO NPs at the later ages tested (PND14 and PND21, but not PND7). In vivo intestinal uptake of CuO NPs and TiO2 E171 was observed by hyperspectral imaging of intestinal cross sections. Brightfield microscopy showed that the number of immune cells increased in the intestinal tissue following NP administration. Orally administered NPs led to low intestinal uptake of NPs and an increase in immune cells in the small and large intestine, suggesting that oral exposure to NPs during early life may lead to irritation or a low-grade inflammation. The long-term impact of increased immune cells in the intestinal tract during early life is unknown.
