title: Oral absorption of PEG-coated versus uncoated gold nanospheres: does agglomeration matter?
abstract: BACKGROUND
  Particle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption.
  
  
  METHODS
  In the study reported here, snapshots of agglomeration behavior of gold nanospheres were evaluated in vivo throughout the gastrointestinal tract using transmission electron microscopy. Agglomeration state within the gastrointestinal tract was then used to help explain differences in gastrointestinal particle absorption, as indicated by tissue levels of gold detected using inductively coupled plasma mass spectrometry. Mice were dosed (10 mg/kg) with either 23 nm PEG-coated or uncoated gold nanospheres.
  
  
  RESULTS
  Transmission electron microscopy demonstrates that PEG-coated gold nanoparticles can be observed as primary, un-agglomerated particles throughout the gastrointestinal tract and feces of dosed animals. In contrast, uncoated gold nanoparticles were observed to form agglomerates of several hundred nanometers in all tissues and feces. Inductively coupled plasma mass spectrometry shows significantly higher levels of gold in tissues from animals dosed with PEG-coated versus uncoated 23 nm gold nanoparticles. Retention of particles after a single oral gavage was also very high, with all tissues of animals dosed with PEG-coated particles having detectable levels of gold at 30 days following exposure.
  
  
  CONCLUSIONS
  Qualitative observation of these particles in vivo shows that dispersed PEG-coated particles are able to reach the absorptive tissues of the intestine while agglomerated uncoated particles are sequestered in the lumen of these tissues. However, the large differences observed for in vivo agglomeration behavior were not reflected in oral absorption, as indicated by gold tissue levels. Additional factors, such as surface chemistry, may have played a more important role than in vivo particle size and should be investigated further.
authors.affiliation: Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA. georgia.hinkley@nih.gov.
authors.forename: Georgia K
authors.initials: GK
authors.lastname: Hinkley
authors.affiliation: Major Analytical and Particle Analysis Instrumentation Center, University of Florida, Box 116400, Gainesville, FL, 32611, USA. pcarp@ufl.edu.
authors.forename: Paul
authors.initials: P
authors.lastname: Carpinone
authors.affiliation: Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA. munson@ufl.edu.
authors.forename: John W
authors.initials: JW
authors.lastname: Munson
authors.affiliation: Particle Engineering Research Center, University of Florida, Box 116135, Gainesville, FL, 32611, USA. kpowers@perc.ufl.edu.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Powers
authors.affiliation: Center for Environmental and Human Toxicology, University of Florida, Box 110885, Gainesville, FL, 32611, USA. smroberts@ufl.edu.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Roberts
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D005750:Gastric Juice / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008813:Mice, Inbred ICR; D046529:Microscopy, Electron, Transmission; D008962:Models, Theoretical; D057145:Nanoshells / Q000008:administration & dosage / Q000737:chemistry*; D065568:Oral Mucosal Absorption / Q000187:drug effects*; D009928:Organ Specificity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D013054:Spectrophotometry, Atomic; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D011092:Polyethylene Glycols; D006046:Gold