Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment
Abstract
:1. Introduction
2. Materials and Methods
2.1. Instrumentation
2.2. Reagents and Materials
2.3. E 171 Samples
2.4. Model Food and E 171-Containing Food Samples
2.5. E 171 Multi-Technique Characterization
2.5.1. TEM
2.5.2. VSSA
2.5.3. DLS and ELS
2.5.4. CLS
2.6. Single-Particle ICP-MS
2.6.1. Instrumental Analysis
2.6.2. E 171 Dispersion Optimization for sp-ICP-MS Analysis
2.7. Fate Studies
2.7.1. Simulated Gastrointestinal Digestion
2.7.2. Lysosomal Digestion
2.7.3. ICP-MS Analytical Measurements
2.8. Statistical Analysis
3. Results
3.1. Pristine Material Characterization
3.1.1. Characterization of the Constituent Particles via TEM and VSSA
3.1.2. Multi-Technique Characterization of E 171 Water Suspensions
3.2. Simulated Gastrointestinal Digestion
3.2.1. Protocol Optimization and Fate Assessment
3.2.2. Agglomeration Behavior in the Intestinal Phase
3.3. Lysosomal Digestion
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Instrumental Parameters | Operating Conditions |
---|---|
Power RF | 1600 W |
Nebulizer | Quartz concentric |
Spray chamber | Cyclonic spray chamber |
Flow nebulizer | 0.99 L min−1 |
Peristaltic pump | −20 rps |
Mode | Standard |
QID | On |
Selected masses | 47Ti, 48Ti |
Dwell time | 100 µs |
Sampling time | 60 s |
Transport efficiency range | 7.51 ± 0.18% |
Density | 3.9 (g cm−3) |
Mass fraction particle/analyte | 1.67 |
Fmin | Fmax | Aspect Ratio | % of constituent Particles with Fmin | % of Mass Fraction with Fmin a | |||||
---|---|---|---|---|---|---|---|---|---|
Median (nm) | Mean (nm) | Median (nm) | Mean (nm) | Median | Mean | <100 nm | <250 nm | <100 nm | <250 nm |
79 | 95 | 114 | 137 | 1.4 | 1.5 | 64 | 98 | 9 | 71 |
Sample | Mean (nm) | D10 (nm) | D50 (Median) (nm) | D99.5 (nm) | Particles <100 nm (%) | Particles <250 nm (%) |
---|---|---|---|---|---|---|
H2O | ||||||
0.1 mg/mL | 191 | 68 | 188 | 505 | 19 | 77 |
0.7 mg/mL | 189 | 77 | 185 | 490 | 17 | 78 |
NaOH 0.1 mM | ||||||
0.1 mg/mL | 190 | 77 | 186 | 488 | 18 | 78 |
0.7 mg/mL | 180 | 73 | 172 | 510 | 20 | 81 |
- | Mean Hydrodynamic Diameter (nm) | Average Intensity (%) | Average PDI | ||
---|---|---|---|---|---|
- | Peak 1 | Peak 2 | Peak 1 | Peak 2 | |
Water (pH 5.5) | 337 ± 142 | 4872 ± 644 | 97.5 | 2.5 | 0.210 |
Citric acid 0.1 M, sodium citrate 0.1 M (pH 2.9) | 373 ± 222 | 4780 ± 712 | 97.9 | 2.1 | 0.251 |
Phosphate buffer 10 mM (pH 7) | 811 ± 316 | 5244 ± 434 | 98.5 | 1.5 | 0.198 |
Sample | Mean Particle Diameter (nm) | D10 (nm) | D50 (Median) (nm) | D99.5 (nm) | Particles <100 nm (%) | Particles <250 nm (%) |
---|---|---|---|---|---|---|
E 171-a—fasted GID | ||||||
0.01 mg/mL, T = 0 | 196 | 90 | 186 | 513 | 14 | 75 |
0.01 mg/mL, T = 30 | 191 | 87 | 178 | 514 | 16 | 77 |
0.1 mg/mL, T = 0 | 198 | 72 | 187 | 535 | 21 | 71 |
0.1 mg/mL, T = 30 | 203 | 75 | 189 | 561 | 20 | 69 |
0.7 mg/mL, T = 0 | 260 | 80 | 256 | 639 | 15 | 48 |
0.7 mg/mL, T = 30 | 265 | 76 | 259 | 659 | 15 | 46 |
E 171-a—fed GID | ||||||
0.01 mg/mL, T = 0 | 181 | 79 | 168 | 509 | 20 | 81 |
0.01 mg/mL, T = 30 | 176 | 74 | 164 | 498 | 24 | 82 |
0.1 mg/mL, T = 0 | 194 | 78 | 187 | 513 | 18 | 75 |
0.1 mg/mL, T = 30 | 191 | 76 | 184 | 519 | 19 | 75 |
0.7 mg/mL, T = 0 | 226 | 92 | 223 | 566 | 12 | 62 |
0.7 mg/mL, T = 30 | 230 | 97 | 226 | 539 | 11 | 61 |
Chocolate candies | ||||||
0.15 mg/mL, T = 0 | 193 | 71 | 173 | 565 | 23 | 73 |
0.15 mg/mL, T = 30 | 193 | 72 | 172 | 578 | 23 | 73 |
Cappuccino | ||||||
0.54 mg/mL, T = 0 | 212 | 94 | 204 | 544 | 12 | 68 |
0.54 mg/mL, T = 30 | 210 | 95 | 199 | 516 | 12 | 68 |
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Ferraris, F.; Raggi, A.; Ponti, J.; Mehn, D.; Gilliland, D.; Savini, S.; Iacoponi, F.; Aureli, F.; Calzolai, L.; Cubadda, F. Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment. Nanomaterials 2023, 13, 1908. https://doi.org/10.3390/nano13131908
Ferraris F, Raggi A, Ponti J, Mehn D, Gilliland D, Savini S, Iacoponi F, Aureli F, Calzolai L, Cubadda F. Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment. Nanomaterials. 2023; 13(13):1908. https://doi.org/10.3390/nano13131908
Chicago/Turabian StyleFerraris, Francesca, Andrea Raggi, Jessica Ponti, Dora Mehn, Douglas Gilliland, Sara Savini, Francesca Iacoponi, Federica Aureli, Luigi Calzolai, and Francesco Cubadda. 2023. "Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment" Nanomaterials 13, no. 13: 1908. https://doi.org/10.3390/nano13131908
APA StyleFerraris, F., Raggi, A., Ponti, J., Mehn, D., Gilliland, D., Savini, S., Iacoponi, F., Aureli, F., Calzolai, L., & Cubadda, F. (2023). Agglomeration Behavior and Fate of Food-Grade Titanium Dioxide in Human Gastrointestinal Digestion and in the Lysosomal Environment. Nanomaterials, 13(13), 1908. https://doi.org/10.3390/nano13131908