Determination of Two Differently Manufactured Silicon Dioxide Nanoparticles by Cloud Point Extraction Approach in Intestinal Cells, Intestinal Barriers and Tissues

Abstract

Food additive amorphous silicon dioxide (SiO2) particles are manufactured by two different methods—precipitated and fumed procedures—which can induce different physicochemical properties and biological fates. In this study, precipitated and fumed SiO2 particles were characterized in terms of constituent particle size, hydrodynamic diameter, zeta potential, surface area, and solubility. Their fates in intestinal cells, intestinal barriers, and tissues after oral administration in rats were determined by optimizing Triton X-114-based cloud point extraction (CPE). The results demonstrate that the constituent particle sizes of precipitated and fumed SiO2 particles were similar, but their aggregate states differed from biofluid types, which also affect dissolution properties. Significantly higher cellular uptake, intestinal transport amount, and tissue accumulation of precipitated SiO2 than of fumed SiO2 was found. The intracellular fates of both types of particles in intestinal cells were primarily particle forms, but slowly decomposed into ions during intestinal transport and after distribution in the liver, and completely dissolved in the bloodstream and kidneys. These findings will provide crucial information for understanding and predicting the potential toxicity of food additive SiO2 after oral intake.

Oral Toxicokinetics, Tissue Distribution, and 28-Day Oral Toxicity of Two Differently Manufactured Food Additive Silicon Dioxides

“…NPs were reported to be more massively absorbed into the bloodstream than bulk-sized particles [ 26 , 27 ]. Our previous study also showed a higher intestinal transport amount of the precipitated SAS than the fumed SAS, using in vitro intestinal barrier models [ 22 ]. It should be noted that the oral absorption of SAS was less than 4%, even at 2000 mg/kg, and this finding is also in good agreement with the previous report [ 28 ].…”

“…The hydrodynamic diameters (375 ± 1 nm) of precipitated SAS in distilled water (DW) were significantly larger than those (156 ± 1 nm) of fumed SAS ( Supplementary Figure S2B ), suggesting high aggregate formation of the former in DW. It is worth noting that precipitated SAS was determined to be less aggregated than fumed SAS in cell culture minimum essential medium and three consecutive steps of the GI fluid ( Figure S2B ) [ 22 ], indicating different aggregate states of SAS depending on the biological environment.…”

“…The low oral absorption and rapid clearance of SAS also suggest its low potential for tissue accumulation and organ burden. On the other hand, SAS particles seem to be absorbed in both particle and ionic forms regardless of manufacturing methods, considering their maximum oral absorption up to 3.9% ( Table 1 ) and in vitro and ex vivo solubilities of 1.8–2.8% in the GI fluids [ 22 ].…”

“…The levels of SAS in biological samples were quantified by measuring total Si concentrations, using ICP–AES (JY2000 Ultrace, HORIBA Jobin Yvon, Longjumeau, France) after microwave digestion, as described in our previous study [ 22 , 38 ]. Briefly, 0.2 g of the sample was transferred to a perfluoroalkoxy alkane vessel, and 6 mL of 70% HNO 3 and 1 mL of 40% HF were added.…”

“…Our previous report demonstrated that the solubility and biological fate of food-additive SAS were dependent on manufacturing methods and biological environments, which were highly affected by aggregate formation under biological conditions [ 22 ]. Precipitated SAS was less aggregated than fumed SAS in cell culture medium and the gastrointestinal (GI) fluid, resulting in high in vitro cellular uptake, intestinal transport using in vitro epithelial barrier models, and tissue distribution level after a single-dose oral administration in rats compared with fumed SAS [ 22 ]; the major fate of SAS was determined to be particle form in human intestinal cells and slowly decomposed into ions during intestinal transport. After a single-dose oral administration in rats, SAS was primarily present as particles in the gastric fluid, but it was mostly in ionic form in the liver, and then only a decomposed ionic form was detected in the kidney.…”