High Potency of SN-38-Loaded Bovine Serum Albumin Nanoparticles Against Triple-Negative Breast Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of sBSANP, BSANP, and Rho-sBSANP
2.3. Characterization of the sBSANPs
2.3.1. Size, Polydispersity Index, Zeta Potential
2.3.2. Particle Yield
2.3.3. Entrapment Efficiency Calculation
2.4. Fluorescence Quenching Study
2.5. FTIR
2.6. In Vitro Release Kinetics
2.7. Ex Vivo Hemolysis Assay
2.8. Cell Culture and Cytotoxicity Assay
2.8.1. Cell Culture
2.8.2. Cytotoxicity Assay
2.9. Cellular Uptake
2.9.1. Flow Cytometry
2.9.2. Confocal Laser Scanning Microscopy
2.10. Annexin V–PI Apoptosis Assay
2.11. Pharmacokinetic Study
2.12. High Performance Liquid Chromatography (HPLC) Analysis
2.12.1. In Vitro Quantitation
2.12.2. In Vivo Quantitation
2.13. Statistical Analysis
3. Results
3.1. Attributes Affecting the Size of Albumin Nanoparticles
3.2. Characterization of sBSANPs
3.2.1. Particle Size, Zeta Potential, Entrapment Efficiency, and Particle Yield
3.2.2. Fluorescence Quenching Study
3.2.3. FTIR
3.3. In Vitro Release Kinetics
3.4. Ex Vivo Hemolysis Assay
3.5. In Vitro Cytotoxicity and Safety Evaluation
3.6. Cellular Uptake
3.7. Annexin V–PI Apoptosis Assay
3.8. Pharmacokinetic Study
4. Discussion
4.1. Attributes Affecting the Size of Albumin Nanoparticles
4.2. Characterization of sBSANP
4.3. In Vitro Release Kinetics
4.4. Ex Vivo Hemolysis Assay
4.5. In Vitro Cytotoxicity and Safety Evaluation
4.6. Pharmacokinetic Study
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Formulation | Particle Size (nm) | PDI | Zeta Potential (mV) | Entrapment Efficiency (%) | Particle Yield (%) |
---|---|---|---|---|---|
sBSANP-F75 | 264.07 ± 13.08 | 0.23 ± 0.01 | −37.16 ± 1.86 | 71.57 ± 0.84 | 86.75 ± 1.53 |
sBSANP-F62.5 | 223.77 ± 2.36 | 0.21 ± 0.04 | −38.30 ± 2.33 | 63.28 ± 0.62 | 81.71 ± 5.49 |
sBSANP-F40 | 134.37 ± 4.48 | 0.22 ± 0.02 | −40.34 ± 0.30 | 59.14 ± 3.14 | 65.91± 0.78 |
BSANP-F75 | 288.23 ± 9.50 | 0.23 ± 0.06 | −41.31 ± 4.76 | - | 91.63 ± 5.51 |
BSANP-F62.5 | 202.03 ± 17.30 | 0.14 ± 0.02 | −53.81 ± 3.39 | - | 85.65 ± 1.43 |
BSANP-F40. | 124.47 ± 1.21 | 0.15 ± 0.04 | −53.16 ± 5.33 | - | 43.02 ± 2.33 |
Cell Lines | IC50 (nM) | |||
---|---|---|---|---|
SN-38 Solution | sBSANP F75 | sBSANP F62.5 | sBSANP F40 | |
MDA-MB-468 | 4.75 ± 0.17 | 3.86 ± 0.85 | 3.65 ± 0.60 | 2.01 ± 0.67 |
MDA-MB-231 | 9.93 ± 3.16 | 4.16 ± 0.75 | 6.82 ± 1.97 | 5.72 ± 1.44 |
MCF-7 | 46.22 ± 9.80 | 26.92 ± 6.30 | 15.94 ± 5.96 | 23.24 ± 6.30 |
Pharmacokinetics Parameters | sBSANP-F62.5 | SN-38 Control | Significance |
---|---|---|---|
Vd (mL) | 1643.78 ± 245.46 | 650.75 ± 64.92 | *** |
CL (mL/h) | 444.14 ± 66.61 | 483.66 ± 80.49 | ns |
AUC (h × ng/mL) | 23.22 ± 3.54 | 21.19 ± 3.11 | ns |
t½ (h) | 7.04 ± 1.38 | 7.35 ± 2.22 | ns |
Cmax (ng/mL) | 6.29 ± 1.06 | 15.54 ± 1.70 | *** |
AUMC (h × h × ng/mL) | 213.54 ± 67.83 | 154.92 ± 67.47 | ns |
MRT (h) | 8.91 ± 1.46 | 7.04 ± 2.57 | ns |
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Share and Cite
Lin, H.-C.; Chuang, C.-H.; Cheng, M.-H.; Lin, Y.-C.; Fang, Y.-P. High Potency of SN-38-Loaded Bovine Serum Albumin Nanoparticles Against Triple-Negative Breast Cancer. Pharmaceutics 2019, 11, 569. https://doi.org/10.3390/pharmaceutics11110569
Lin H-C, Chuang C-H, Cheng M-H, Lin Y-C, Fang Y-P. High Potency of SN-38-Loaded Bovine Serum Albumin Nanoparticles Against Triple-Negative Breast Cancer. Pharmaceutics. 2019; 11(11):569. https://doi.org/10.3390/pharmaceutics11110569
Chicago/Turabian StyleLin, Hsin-Che, Chih-Hung Chuang, Meng-Hsuan Cheng, Yu-Chih Lin, and Yi-Ping Fang. 2019. "High Potency of SN-38-Loaded Bovine Serum Albumin Nanoparticles Against Triple-Negative Breast Cancer" Pharmaceutics 11, no. 11: 569. https://doi.org/10.3390/pharmaceutics11110569