Rapid Kinetics of Size and pH-Dependent Dissolution and Aggregation of Silver Nanoparticles in Simulated Gastric Fluid

Abstract

As silver nanoparticles (AgNPs) are used in a wide array of commercial products and can enter the human body through oral exposure, it is important to understand the fundamental physical and chemical processes leading to changes in nanoparticle size under the conditions of the gastrointestinal (GI) tract. Rapid AgNP growth was observed using nanoparticle tracking analysis with 30 s resolution over a period of 17 min in simulated gastric fluid (SGF) to explore rapid kinetics as a function of pH (SGF at pH 2, 3.5, 4.5 and 5), size (20 and 110 nm AgNPs), and nanoparticle coating (citrate and PVP). Growth was observed for 20 nm AgNP at each pH, decreasing in rate with increasing pH, with the kinetics shifting from second-order to first-order. The 110 nm AgNP showed growth at ≤3.5 pH, with no growth observed at higher pH. This behavior can be explained by the generation of Ag⁺ in acidic environments, which precipitates with Cl^-, leading to particle growth and facilitating particle aggregation by decreasing their electrostatic repulsion in solution. These results highlight the need to further understand the importance of initial size, physicochemical properties, and kinetics of AgNPs after ingestion to assess potential toxicity.

Figure 1

A diagram depicting (left) a series of overlaid number size distributions as a function of time and (right) a plot of time versus diameter with concentration as color. The 3-D plot (middle) shows the relationship between each plot and the benefits of time on the x-axis for monitoring dissolution and aggregation as a function of time. Arrows indicate the plane of the 3-D image being used for each plot.

Figure 2

Image plots for Citrate 20, PVP 20, Citrate 110, and PVP 110 showing changes in particulate size and concentration over time for each SGF pH examined. The gray bar in each graph indicates time in which there was no sizing data.

Figure 3

(a) Absolute and (b) percent change from original diameter at each SGF pH. Error bars are present; however, the calculated error is smaller than the width of the graph markers for some points, making the bars difficult to observe.

Figure 4

Schematic of AgNP interactions in acidic SGF media using the example of citrate which is stabilized by electrostatic repulsion. PVP would stabilize via steric hindrance but would also be stripped off in acidic solution resembling this mechanism.

Figure 5

EDX spectra of the core and the precipitated AgCl coating for a PVP 110 aggregate in pH 2 SGF, along with elemental mapping of Ag (red) and Cl (aqua) in the inset.

Figure 6

ZP of capped AgNP in acidic, neutral, and salt solutions and bare AgNP in acidic and neutral solutions to determine their isoelectric pH (ZP = 0). Theoretical ZP measurements for PVP 20 and PVP 110 nm particles in SGF (particle + HCl + NaCl) were calculated to provide isoelectric pHs of PVP 20 and PVP 110 in SGF (solid marks at zero line). Solid lines and markers are experimental data, while dashed lines are theoretical.

Figure 7

Particle (a) loss and (b) growth rates for each AgNP in varying SGF pH and in water (pH 6). The negative sign of the particle loss rates indicate loss of nanoparticles.

Figure 8

TEM images of 20 nm (yellow) AgNP and SEM images of 110 nm (green) AgNP after being digested in SGF of pH 2 (red) and pH 5 (blue) for a period of 10 min. Elemental mapping (right) using TEM/EDX (purple) shows the distribution of these elements on the particles.

Figure 9

Cartoon schematic of the predicted processing of AgNP in the human stomach using Citrate 20 in pH < 2 during the first 10 min after ingestion as an example. The forms of silver include initial single AgNPs (AgNP₀), free Ag⁺ ions, AgCl precipitate, and aggregated particulates (AgNP_agg). Initial data (markers) and data for AgNP₀ and AgNP_agg are solid lines. Inferred data for Ag⁺, AgCl, and time 0.1–2 min for AgNP₀ and AgNP_agg are shown as dashed lines.