Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Drug-Free Niosomes Preparation and Optimization
2.2. Optimization of the Prepared Drug-Free Niosomes
2.3. Preparation and Evaluation of Drug-Loaded Niosomes
2.4. In Vitro Drug Release
2.5. Transmission Electron Microscopy (TEM)
2.6. Evaluation of the Anticancer Activity
2.6.1. Cytotoxicity Study against HT-29 Cells
2.6.2. Apoptosis Analysis
3. Materials and Methods
3.1. Materials
3.2. Experimental Design
3.3. Preparation of Drug-Free Niosomes
3.4. Particle Size and Z-Potential Analysis
3.5. Preparation of Drug-Loaded Niosomes
3.6. Evaluation of the Prepared Drug-Loaded Niosomes
3.6.1. Drug Entrapment Efficiency (EE%)
3.6.2. Measurement of the Particle Size and Z-Potential of Drug-Loaded Niosomes
3.6.3. In Vitro Drug Release Study
3.6.4. Transmission Electron Microscopy (TEM)
3.7. Evaluation of the Anticancer Activity for the Selected Paclitaxel-Niosomes and Oxaliplatin-Niosomes
3.7.1. Cytotoxicity Study against HT-29 Cells
3.7.2. Cell Apoptosis and Cell Cycle Assay of HT-29 Cells
3.8. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Runs | Factors (Independent Variables) | Responses (Dependent Variables) | ||||
---|---|---|---|---|---|---|
CHOL Ratio (w/w) | Surfactant Ratio (w/w) | Surfactant Type * | Particle Size (nm) | Z-Potential (mV) | PDI | |
F1 | 1.00 | 3.00 | Span 60 | 242.5 ± 22.4 | (−) 29.3 ± 1.8 | 0.158 ± 0.01 |
F2 | 1.00 | 4.00 | Span 60 | 198.2 ± 18.6 | (−) 31.4 ± 1.6 | 0.214 ± 0.04 |
F3 | 1.50 | 3.25 | Span 60 | 232.1 ± 15.7 | (−) 30.4 ± 2.1 | 0.256 ± 0.11 |
F4 | 2.00 | 3.00 | Span 60 | 293.3 ± 17.2 | (−) 30.2 ± 1.7 | 0.247 ± 0.21 |
F5 | 2.00 | 4.00 | Span 60 | 251.2 ± 20.3 | (−) 32.1 ± 1.9 | 0.165 ± 0.06 |
F6 | 1.00 | 3.00 | TPGS | 265.3 ± 18.4 | (−) 29.1 ± 1.7 | 0.146 ± 0.04 |
F7 | 1.00 | 3.50 | TPGS | 241.2 ± 16.7 | (−) 30.2 ± 2.2 | 0.132 ± 0.03 |
F8 | 1.50 | 3.00 | TPGS | 231.5 ± 18.2 | (−) 29.8 ± 2.4 | 0.189 ± 0.14 |
F9 | 2.00 | 4.00 | TPGS | 194.4 ± 15.5 | (−) 31.8 ± 1.9 | 0.175 ± 0.20 |
F10 | 2.00 | 3.00 | TPGS | 221.2 ± 21.3 | (−) 30.2 ± 1.6 | 0.211 ± 0.07 |
F11 | 2.00 | 3.50 | TPGS | 198.1 ± 17.8 | (−) 31.5 ± 1.8 | 0.241 ± 0.31 |
F12 | 1.00 | 4.00 | Tween 80 | 241.7 ± 19.8 | (−) 30.6 ± 2.4 | 0.257 ± 0.45 |
F13 | 1.00 | 3.00 | Tween 80 | 261.4 ± 22.6 | (−) 28.8 ± 2.1 | 0.237 ± 0.25 |
F14 | 1.50 | 3.00 | Tween 80 | 228.3 ± 19.5 | (−) 28.9 ± 1.5 | 0.198 ± 0.41 |
F15 | 1.50 | 3.50 | Tween 80 | 203.1 ± 17.9 | (−) 30.3 ± 1.8 | 0.269 ± 0.09 |
F16 | 2.00 | 4.00 | Tween 80 | 189.2 ± 13.4 | (−) 31.5 ± 2.2 | 0.222 ± 0.17 |
F17 | 2.00 | 3.00 | Tween 80 | 228.4 ± 16.4 | (−) 30.7 ± 2.1 | 0.243 ± 0.29 |
Source | Particle Size (nm) | Z-Potential (mV) | ||
---|---|---|---|---|
F | p-Value | F | p-Value | |
Model | 68.78 | <0.0001 | 12.67 | 0.0058 |
A: CHOL ratio | 23.40 | 0.0047 | 33.52 | 0.0022 |
B: Surfactant ratio | 236.62 | <0.0001 | 92.89 | 0.0002 |
C: Surfactant type | 31.81 | 0.0014 | 3.40 | 0.1168 |
AB | 1.86 | 0.2313 | 1.17 | 0.3288 |
AC | 178.48 | <0.0001 | 0.78 | 0.5055 |
BC | 3.05 | 0.1359 | 0.85 | 0.4817 |
A^2 | 49.58 | 0.0009 | 0.56 | 0.4872 |
B^2 | 12.94 | 0.0156 | 0.32 | 0.5939 |
Adequate precision | 29.912 | 12.934 | ||
R2 | 0.9934 | 0.9654 | ||
Adjusted R2 | 0.9790 | 0.8892 | ||
Predicted R2 | 0.8413 | 0.5883 | ||
SD | 4.11 | 0.34 | ||
%CV | 1.78 | 1.12 |
Drug Loaded (Molar Ratio) | Oxaliplatin–TPGS Niosomes | Paclitaxel–TPGS Niosomes | ||||||
---|---|---|---|---|---|---|---|---|
EE% | Particle Size (nm) | Z-Potential (mV) | PDI | EE% | Particle Size (nm) | Z-Potential (mV) | PDI | |
0.5 | 77.19 ±2.68 | 236.4 ± 22.3 | −31.7 ± 0.96 | 0.236 ± 0.07 | 83.82 ± 3.13 | 227.4 ± 16.3 | −30.91 ± 0.45 | 0.283 ± 0.04 |
1 | 90.57 ±2.05 | 278.5 ± 19.7 | −32.7 ± 1.01 | 0.264 ± 0.05 | 93.51 ± 2.97 | 251.6 ± 18. 1 | −31.69 ± 0.98 | 0.273 ± 0.08 |
2 | 91.03 ±2.80 | 285.8 ± 23.5 | −33.25 ± 1.41 | 0.295 ± 0.07 | 93.31 ± 3.31 | 258.6 ± 13.3 | −32.99 ± 1.08 | 0.287 ± 0.09 |
Formulation | Correlation Coefficient (R2) | |||
---|---|---|---|---|
Zero Order | 1st Order | Higuchi Diffusion | Korsmeyer–Peppas | |
Oxaliplatin–TPGS–niosomes | 0.6114 ± 0.034 | 0.8715 ± 0.027 | 0.8871 ± 0.021 | 0.8844 ± 0.011 |
Paclitaxel–TPGS–niosomes | 0.7164 ± 0.021 | 0.9006 ± 0.014 | 0.9475 ± 0.011 | 0.942 ± 0.015 |
Factors | Levels | ||
---|---|---|---|
Low (−1)–High (1) | |||
A (X1): Cholesterol (molar ratio) | 3 | 3.5 | 4 |
B (X2): Surfactant (molar ratio) | 1 | 1.5 | 2 |
C (X3): Surfactant type | Span 60 | TPGS | Tween 80 |
Responses | |||
(Y1): Particle size (PS) | Minimize | ||
(Y2): Zeta potential (Z-potential) | Maximize |
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El-Far, S.W.; Abo El-Enin, H.A.; Abdou, E.M.; Nafea, O.E.; Abdelmonem, R. Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies. Pharmaceuticals 2022, 15, 816. https://doi.org/10.3390/ph15070816
El-Far SW, Abo El-Enin HA, Abdou EM, Nafea OE, Abdelmonem R. Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies. Pharmaceuticals. 2022; 15(7):816. https://doi.org/10.3390/ph15070816
Chicago/Turabian StyleEl-Far, Shaymaa Wagdy, Hadel A. Abo El-Enin, Ebtsam M. Abdou, Ola Elsayed Nafea, and Rehab Abdelmonem. 2022. "Targeting Colorectal Cancer Cells with Niosomes Systems Loaded with Two Anticancer Drugs Models; Comparative In Vitro and Anticancer Studies" Pharmaceuticals 15, no. 7: 816. https://doi.org/10.3390/ph15070816