Oral absorption of PEG-coated versus uncoated gold nanospheres: does agglomeration matter?

Abstract

BackgroundParticle 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.MethodsIn 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.ResultsTransmission 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.ConclusionsQualitative 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.

Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats

“…If biliary excretion of a nanoparticle is substantial, this can result in an underestimation of oral bioavailability from urinary and fecal measurements. Also, there is evidence that ingested nanoparticles can become trapped within the gastrointestinal tract, neither absorbed systemically nor excreted in feces for a month or more after an oral dose (Hinkley et al, 2015). This too can lead to errors in bioavailability assessment from fecal measurements, at least in theory.…”

“…PEG coating can also be important in reducing agglomeration of ingested AuNPs within the GI tract. Native (uncoated) AuNPs were found to agglomerate rapidly and extensively when given orally to mice, while PEG-coated AuNPs remained dispersed as primary particles throughout GI transit (Hinkley et al, 2015).…”

“…There are few studies investigating the oral absorption of coated or uncoated AuNPs (Hillyer & Albrecht, 2001;Schleh et al, 2012;Smith et al, 2013;Hinkley et al, 2015). All of these studies evaluated AuNP bioavailability with approaches that involved measurement of gold in tissues and/or excreta (urine, feces).…”

“…Gold nanoparticles (AuNPs) also have properties that simplify to some extent the study of their pharmacokinetics. They have low dissolution in biological environments, including the gastrointestinal tract (Hinkley et al, 2015), and the background concentrations of gold in tissues are low. As a result, AuNPs can be quantified relatively easily in tissues simply by digesting tissue samples and measuring the gold content, and the high electron density of gold enhances visualization of the nanoparticles in tissues with electron microscopy.…”

In vivo testing of gold nanoparticles using the Caenorhabditis elegans model organism

“…Studies in superior animal models reported scarce or no translocation of gold nanoparticles after oral administration depending on the dosing regime, NP size and surface properties but without a clear trend. [66,67] Therefore, we believe NP size can also have an influence in C. elegans, together with the exposure concentration and the presence/absence of recovery time.…”