Research ArticlesGastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles
Section snippets
INTRODUCTION
It is generally accepted that the uptake of insoluble, particulate matter through the digestive tract occurs in low quantities, and that the pathway and amount of particle uptake is size dependent.1,2 Research on the passage of microparticles through the gut lumen into the body has shown that particles in the micrometer size range enter the body by a process called persorption: the paracellular uptake of microparticles from the digestive tract into the body.3 Extensive work has been done on the
MATERIALS AND METHODS
We have previously described in detail the methodology and correlative use of transmission electron microscopy (TEM) and instrumental neutron activation analysis (INAA) in the qualitative and quantitative detection of colloidal gold spheres in biological specimens.28,29
INAA
INAA was used to quantitate the amount of gold that had crossed the gastrointestinal tract and localized to tissues/organs. Blood, brain, lung, heart, kidney, spleen, liver, small intestine, and stomach samples were collected and placed in trace‐element free 2/5 dram polyethylene flip‐top vials. Samples were sealed by friction welding and exposed for 7200 s while rotating to a thermal neutron flux of 1 × 1013 neutrons/cm2 s using a 1 MW TRIGA open pool reactor at the University of
TEM
TEM was used to determine the location and pathway of particle uptake across the gastrointestinal tract. Representative portions of the stomach, jejunum, proximal ileum, distal ileum, Peyer's patch, and colon of experimental and normal (control) animals were fixed in 2% glutaraldehyde, 2% formaldehyde in 0.1 M phosphate buffer for 2 h at room temperature. Samples were then rinsed with buffer, dehydrated through a graded ethanol series, and cleared with propylene oxide. Samples were then
INAA
Gold levels in tissues of mice orally fed a 4, 10, 28, or 58 nm diameter colloidal gold particle suspension are presented in Table 1. Smaller colloidal gold particles were able to cross the gut and localize to tissues more readily than larger particles. In general, tissues for which gold quantitation was done showed a step‐wise drop in gold deposition levels as particle size was increased from 4 to 58 nm in size.
In animals given 4, 10, and 28 nm diameter colloidal gold particles, gold levels
TEM
Four and ten nm diameter colloidal gold particle uptake across the gut was seen to occur by persorption through single enterocytes that had died and were in the process of being extruded from a villus (Figures 1 and 2). Persorption was seen to occur in the tips and lateral sides of villi in the proximal ileum, distal ileum, and in Peyer's patch regions of the small intestine. Individual particles, as well as small clusters, could be found in the gastrointestinal lumen and followed from the dead
DISCUSSION
Here we have shown the persorption and distribution of nanometer‐sized colloidal gold particles following oral administration. Previous reports of nanoparticle uptake have shown uptake to occur in the Peyer's patch regions of the small intestine, with little translocation occurring through nonlymphoid gut tissue.15., 16., 17., 18. Other studies have shown particles to be taken up by persorption. These studies have shown uptake of micrometer‐sized particles by persorption through breaks in the
Acknowledgements
This work was supported in part by a National Science Foundation Minority Graduate Research Fellowship. We are grateful to Richard Cashwell, director of the University of Wisconsin‐Madison Nuclear Reactor Laboratory, and Randall Massey, director of the University of Wisconsin‐Madison Medical School Electron Microscope Facility. We also thank Paul Sims and Victor Anaya‐Báez for assistance in preparing samples for INAA. Useful discussions with Dr. Allen Clark, Dr. Joseph Robinson, Sy‐Juen Wu, and
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