Research Articles
Gastrointestinal persorption and tissue distribution of differently sized colloidal gold nanoparticles

https://doi.org/10.1002/jps.1143Get rights and content

Abstract

The gastrointestinal uptake of micro‐ and nanoparticles has been the subject of recent efforts to develop effective carriers that enhance the oral uptake of drugs and vaccines. Here, we used correlative instrumental neutron activation analysis and electron microscopy to quantitatively and qualitatively study the gastrointestinal uptake and subsequent tissue/organ distribution of 4, 10, 28, and 58 nm diameter metallic colloidal gold particles following oral administration to mice. In our quantitative studies we found that colloidal gold uptake is dependent on particle size: smaller particles cross the gastrointestinal tract more readily. Electron microscopic studies showed that particle uptake occurred in the small intestine by persorption through single, degrading enterocytes in the process of being extruded from a villus. To our knowledge this is the first report, at the ultrastructural level, of gastrointestinal uptake of particulates by persorption through holes created by extruding enterocytes. © 2001 Wiley‐Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1927–1936, 2001

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

REFERENCES (31)

  • G. Fabian

    Persorption—the way of large sized corpuscle particles via the lymphatic system

    Lymphology

    (1983)
  • G. Volkheimer et al.

    Persorption of metallic iron particles

    Gut

    (1969)
  • H.J. Schneider et al.

    Studies of the persorption of large particles from radio‐labelled cation exchangers

    Urol Int

    (1983)
  • G. Volkheimer

    Hematogenous dissemination of ingested polyvinyl chloride particles

    Ann NY Acad Sci

    (1975)
  • G. Volkheimer et al.

    The phenomenon of persorption

    Digestion

    (1968)
  • Cited by (0)

    View full text