Influence of Pre-Dispersion Media on the Batch Reactor Dissolution Behavior of Al2O3 Coated TiO2 (NM-104) and Two ZnO (NM-110 and NM-111) Nanomaterials in Biologically Relevant Test Media

Abstract

Dissolution plays an important role on pulmonary toxicity of nanomaterials (NMs). The influence of contextual parameters on the results from dissolution testing needs to be identified to improve the generation of relevant and comparable data. This study investigated how pre-dispersions made in water, low-calcium Gamble’s solution, phagolysosomal simulant fluid (PSF), and 0.05% bovine serum albumin (BSA) affected the dissolution of the Al2O3 coating on poorly soluble TiO2 also coated with glycerine (NM-104) and rapidly dissolving uncoated (NM-110) and triethoxycaprylsilane-coated ZnO (NM-111) NMs. Dissolution tests were undertaken and controlled in a stirred batch reactor using low-calcium Gamble’s solution and phagolysosomal simulant fluid a surrogate for the lung-lining and macrophage phagolysosomal fluid, respectively. Pre-dispersion in 0.05% BSA-water showed a significant delay or decrease in the dissolution of Al2O3 after testing in both low-calcium Gamble’s solution and PSF. Furthermore, use of the 0.05% BSA pre-dispersion medium influenced the dissolution of ZnO (NM-110) in PSF and ZnO (NM-111) in low-calcium Gamble’s solution and PSF. We hypothesize that BSA forms a protective coating on the particles, which delays or lowers the short-term dissolution of the materials used in this study. Consequently, the type of pre-dispersion medium can affect the results in short-term dissolution testing.

Dissolution Behaviour of Metal-Oxide Nanomaterials in Various Biological Media

“…All ENMs tested displayed increased dissolution in PSF compared to Gamble ( Figure 3 ) due to the higher hydrogen ion concentration in PSF [ 42 , 43 , 44 , 46 ]. These results are in agreement with previous studies [ 22 , 69 , 70 ]. The low solubility of ZnO ENM in near-neutral Gamble (4.6%, 3.71 mg/L) observed in our study may be indicative of biodurability and accumulation in the interstitial lung environment.…”

“…The latter observation suggests that dissolution may be the main process defining this ENM’s fate in the lungs, with released ions rather than undissolved particles causing the observed effects. Holmfred et al [ 69 ] observed a rapid 10-fold higher solubility in PSF (exceeding the nominal dose of 102 mg/L) compared to low-calcium Gamble medium for ZnO ENM (NM-110). The dissolution half-time of ZnO nanoparticles in PSF media was found to be short (t 1/2 < 1 h), suggesting that clearance is dominated by dissolution and effects from released ions for this ENM [ 22 ].…”

Acute phase response following pulmonary exposure to soluble and insoluble metal oxide nanomaterials in mice

“…The electrical mobility sizes of the agglomerated particles produced were measured online during spark ablation system using a Scanning Mobility Particle Sizer (SMPS), consisting of Differential Mobility Analyzer (TSI, Model 3085), and a Condensation Particle Counter (TSI Model 3025). The specific surface area of the metal oxide powders was analyzed using the BET nitrogen absorption NMs was determined by dissolution in phagolysosomal simulant fluid (PSF) (pH = 4.5), using an Atmosphere-Temperature-pHcontrolled Stirred Batch Reactor (ATempH SBR) as described by Holmfred et al [40]. NMs were first prewetted with 0.5% ethanol, followed by their dispersion in 0.05% BSA water to a concentration of 1.25 g/L and sonication, as described previously.…”

“…300 m 2 /g. Dissolution of Al 2 O 3 and SnO 2 in PSF was determined using a ATempH SBR [40]. No dissolution of SnO 2 was detected in PSF within the 24 h period of the analysis.…”

“…Detailed information of dissolution profiles are found in the Additional file 1. For ZnO and TiO 2 , PSF solubility values of the same substances were tested in Holmfred et al [40] using the same approach. For ZnO, the solubility limit was higher than 100 mg/L (used test concentration) and for TiO 2 no dissolution was observed.…”