Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of CCG-211790 Nanosuspensions
2.3. Dynamic Light Scattering (DLS)
2.4. Scanning Electron Microscopy
2.5. High-Performance Liquid Chromatography (HPLC) Analysis of Nanosuspensions
2.6. Stability of CCG-211790 Nanosuspensions
2.7. In Vitro Dissolution Study
2.8. Pilot PK Study of CCG-211790 Powder Suspension
2.9. PK Studies of Nanosuspensions
2.10. UPLC-MS/MS Analysis of Plasma Samples
2.11. Statistics
3. Results
3.1. Particle Size and Morphology
3.2. Storage Stability of Nanosuspensions
3.3. In Vitro Dissolution Studies
3.4. Pilot PK Studies
3.5. PK Studies
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Duration (Week) | Z-Average (nm) | Polydispersity Index | Zeta Potential (mV) | |||
---|---|---|---|---|---|---|
4 °C | RT | 4 °C | RT | 4 °C | RT | |
0 | 315 ± 6 | 315 ± 6 | 0.18 ± 0.03 | 0.18 ± 0.03 | −42.3 ± 4.2 | −42.3 ± 4.2 |
1 | 311 ± 1 | 310 ± 3 | 0.21 ± 0.01 | 0.22 ± 0.01 | −49.3 ± 0.5 | −48.4 ± 0.3 |
2 | 309 ± 3 | 316 ± 7 | 0.20 ± 0.03 | 0.20 ± 0.03 | −49.4 ± 1.3 | −49.5 ± 0.9 |
4 | 314 ± 2 | 322 ± 6 | 0.21 ± 0.01 | 0.23 ± 0.01 | −46.1 ± 0.4 | −52.3 ± 0.7 |
6 | 315 ± 3 | 319 ± 5 | 0.21 ± 0.01 | 0.20 ± 0.03 | −45.4 ± 0.4 | −51.3 ± 0.3 |
Duration (Week) | Z-Average (nm) | Polydispersity Index | Zeta Potential (mV) | |||
---|---|---|---|---|---|---|
4 °C | RT | 4 °C | RT | 4 °C | RT | |
0 | 915 ± 24 | 915 ± 24 | 0.52 ± 0.03 | 0.52 ± 0.03 | −42.2 ± 0.2 | −42.2 ± 0.2 |
1 | 900 ± 99 | 947 ± 60 | 0.58 ± 0.12 | 0.62 ± 0.02 * | −49.5 ± 0.5 * | −50.4 ± 0.7 * |
2 | 911 ± 37 | 912 ± 66 | 0.61 ± 0.01 * | 0.62 ± 0.07 | −44.9 ± 0.6 * | −49.1 ± 0.7 * |
4 | 966 ± 89 | 878 ± 17 | 0.59 ± 0.03 | 0.54 ± 0.04 | −47.7 ± 1.0 * | −50.2 ± 0.3 * |
6 | 856 ± 17 * | 891 ± 24 | 0.57 ± 0.05 | 0.60 ± 0.05 | −46.4 ± 1.4 * | −50.0 ± 1.5 * |
PK Parameters | Pilot Study for IV |
---|---|
Cmax (mg L−1) | 1.21 ± 0.15 |
AUC0∓∞ (mg L−1 h) | 0.67 ± 0.18 |
MRT0∓∞ (h) | 0.95 ± 0.07 |
t1/2β (h) | 1.44 ± 0.15 |
Vz (L kg−1) | 8.07 ± 2.92 |
CL (L h−1 kg−1) | 3.85 ± 1.01 |
PK Parameters | Pilot Study for PO |
---|---|
Cmax (mg L−1) | 0.04 ± 0.01 |
Tmax (h) | 1.50 ± 0.71 |
AUC0∓∞ (mg L−1 h) | 0.18 ± 0.03 |
MRT0∓∞ (h) | 4.75 ± 1.20 |
t1/2β (h) | 3.88 ± 1.68 |
Vz /F (L kg−1) | 168 ± 101 |
CL/F (L h−1 kg−1) | 28.8 ± 5.6 |
FIV | 13.4% |
PK Parameters | PEG/PG | NanoA | NanoB |
---|---|---|---|
Cmax (mg L−1) | 1.63 ± 0.25 | 1.31 ± 0.55 | 1.07 ± 0.44 * |
AUC0∓∞ (mg L−1 h) | 1.11 ± 0.14 | 0.64 ± 0.19 * | 0.49 ± 0.12 * |
MRT0∓∞ (h) | 0.98 ± 0.17 | 0.90 ± 0.14 | 0.77 ± 0.21 |
t1/2β (h) | 1.13 ± 0.27 | 1.08 ± 0.18 | 1.06 ± 0.27 |
Vz (L kg−1) | 3.66 ± 0.93 | 6.44 ± 1.84 * | 8.37 ± 3.29 * |
CL (L h−1 kg−1) | 2.28 ± 0.27 | 4.21 ± 1.28 * | 5.28 ± 1.01 * |
PK Parameters | Coconut Oil | NanoA | NanoB |
---|---|---|---|
Cmax (mg L−1) | 0.12 ± 0.07 | 0.13 ± 0.05 | 0.12 ± 0.03 |
Tmax (h) | 2.33 ± 0.82 | 1.58 ± 1.28 | 1.08 ± 0.49 * |
AUC0∓∞ (mg L−1 h) | 0.63 ± 0.27 | 0.63 ± 0.17 | 0.50 ± 0.08 |
MRT0∓∞ (h) | 6.59 ± 3.22 | 5.00 ± 1.14 | 4.34 ± 1.03 |
t1/2β (h) | 3.82 ± 2.23 | 3.24 ± 1.36 | 2.61 ± 0.45 |
Vz /F (L kg−1) | 46.1 ± 24.6 | 41.1 ± 21.7 | 38.2 ± 8.9 |
CL/F (L h−1 kg−1) | 8.99 ± 3.14 | 8.53 ± 2.88 | 10.14 ± 1.64 |
FPEG/PG | 28.4% | 28.6% | 22.7% |
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Wang, N.; Qi, F.; He, X.; Shi, H.; Anderson, D.W.; Li, H.; Sun, H. Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions. Pharmaceutics 2021, 13, 1586. https://doi.org/10.3390/pharmaceutics13101586
Wang N, Qi F, He X, Shi H, Anderson DW, Li H, Sun H. Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions. Pharmaceutics. 2021; 13(10):1586. https://doi.org/10.3390/pharmaceutics13101586
Chicago/Turabian StyleWang, Nan, Feng Qi, Xiaolong He, Honglan Shi, David W. Anderson, Hao Li, and Hongmin Sun. 2021. "Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions" Pharmaceutics 13, no. 10: 1586. https://doi.org/10.3390/pharmaceutics13101586
APA StyleWang, N., Qi, F., He, X., Shi, H., Anderson, D. W., Li, H., & Sun, H. (2021). Preparation and Pharmacokinetic Characterization of an Anti-Virulence Compound Nanosuspensions. Pharmaceutics, 13(10), 1586. https://doi.org/10.3390/pharmaceutics13101586