Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies
Abstract
:1. Introduction
2. Results and Discussion
2.1. Optimization
2.2. Impact of Independent Variables X1, X2, and X3 on Particle Size (Y1)
2.3. Impact of Independent Variables X1, X2, and X3 on %Drug Encapsulation (Y2)
2.4. Impact of Independent Variables X1, X2, and X3 on %Cumulative Drug Release (Y3)
2.5. Checkpoint Analysis of Optimum Formulation
2.6. Characterization of Nanosystem
2.6.1. Nanoparticlecharacterization
2.6.2. Thermal Behavior
2.6.3. FT-IR Spectral Analysis
2.6.4. Drug Release and Kinetics
2.6.5. Everted Gut Sac Model
2.6.6. Cell-Viability Assay
2.6.7. Antioxidant Activity
2.6.8. Stability Study
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Analytical Methodology
4.3. Formulation Optimization
4.4. Preparation of β-Sitosterol-Loaded Alg/Ch-NPs
4.5. Folate Modification of β-Sitosterol-Loaded Alg/Ch-NPs
4.6. In Vitro Characterization of Nanosize System
4.6.1. Particle Sizes and Their Distribution
4.6.2. Drug Encapsulation and Loading
4.6.3. Fourier Transform Infrared Spectroscopy (FT-IR)
4.6.4. Differential Scanning Calorimetry
4.6.5. Drug-Release Study
4.6.6. In Vitro Permeation Study
4.6.7. Cell-Viability Study
4.6.8. Radical Scavenging Power
4.7. Stability Study
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Independent Variables | Level Employed | ||
---|---|---|---|
Low (−1) | Medium (0) | High (+1) | |
X1: Chitosan (% w/v) | 0.1 | 0.2 | 0.3 |
X2: Sodium alginate (% w/v) | 0.2 | 0.4 | 0.6 |
X3: Calcium chloride (mM) | 16 | 24 | 32 |
Dependent Variables | |||
Y1: Particle size (nm) | Minimize | ||
Y2: Drug encapsulation (%) | Maximize | ||
Y3: Drug release (%) | Maximize |
Formulation Code | Independent Variables | Responses | ||||
---|---|---|---|---|---|---|
X1 (% w/v) | X2 (% w/v) | X3 (mM) | Y1 (nm) | Y2 (%) | Y3 (%) | |
FN1 | 0.10 | 0.40 | 16.00 | 121 | 90 | 70 |
*FN2 | 0.20 | 0.40 | 24.00 | 142 | 72 | 49 |
FN3 | 0.30 | 0.60 | 24.00 | 166 | 80 | 54 |
FN4 | 0.10 | 0.20 | 24.00 | 151 | 86 | 55 |
*FN5 | 0.20 | 0.40 | 24.00 | 137 | 73 | 47 |
FN6 | 0.20 | 0.60 | 16.00 | 170 | 87 | 37 |
*FN7 | 0.20 | 0.40 | 24.00 | 145 | 74 | 49 |
FN8 | 0.10 | 0.60 | 24.00 | 123 | 93 | 74 |
FN9 | 0.30 | 0.40 | 32.00 | 146 | 72 | 72 |
FN10 | 0.20 | 0.60 | 32.00 | 168 | 75 | 52 |
FN11 | 0.20 | 0.20 | 16.00 | 139 | 78 | 40 |
*FN12 | 0.20 | 0.40 | 24.00 | 140 | 74 | 48 |
FN13 | 0.10 | 0.40 | 32.00 | 149 | 70 | 77 |
FN14 | 0.20 | 0.20 | 32.00 | 180 | 78 | 38 |
*FN15 | 0.20 | 0.40 | 24.00 | 146 | 71 | 47 |
FN16 | 0.30 | 0.40 | 16.00 | 138 | 67 | 58 |
FN17 | 0.30 | 0.20 | 24.00 | 131 | 79 | 58 |
Model | R2 | Adjusted R2 | Predicted R2 | SD | CV % | Desirability |
---|---|---|---|---|---|---|
Response: Y1 | 0.958 | |||||
Quadratic | 0.9805 | 0.9554 | 0.8706 | 3.45 | 2.35 | |
2FI | 0.5886 | 0.3417 | −0.9643 | 13.25 | ||
Linear | 0.2245 | 0.0456 | −0.5873 | 15.96 | ||
Response: Y2 | 0.958 | |||||
Quadratic | 0.9904 | 0.9780 | 0.9565 | 1.11 | 1.42 | |
2FI | 0.5934 | 0.3494 | −0.5409 | 6.01 | ||
Linear | 0.3668 | 0.2207 | −0.1936 | 6.58 | ||
Response: Y3 | 0.958 | |||||
Quadratic | 0.9943 | 0.9870 | 0.9326 | 1.41 | 3.46 | |
2FI | 0.23391 | −0.2174 | −2.5687 | 13.70 | ||
Linear | 0.1440 | −0.0536 | −0.7143 | 12.69 |
Independent Variables | Optimized Composition | Observed Responses | Predicted Response | ||||
---|---|---|---|---|---|---|---|
Y1 (nm) | Y2 (%) | Y3 (%) | Y1 (nm) | Y2 (%) | Y3 (%) | ||
X1:X2:X3 | 0.1%:0.48%:16.32 mM | 126 ± 8.70 | 91.06 ± 2.6 | 71.50 ± 6.5 | 121 | 93 | 72.21 |
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Karim, S.; Akhter, M.H.; Burzangi, A.S.; Alkreathy, H.; Alharthy, B.; Kotta, S.; Md, S.; Rashid, M.A.; Afzal, O.; Altamimi, A.S.A.; et al. Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies. Gels 2022, 8, 219. https://doi.org/10.3390/gels8040219
Karim S, Akhter MH, Burzangi AS, Alkreathy H, Alharthy B, Kotta S, Md S, Rashid MA, Afzal O, Altamimi ASA, et al. Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies. Gels. 2022; 8(4):219. https://doi.org/10.3390/gels8040219
Chicago/Turabian StyleKarim, Shahid, Md Habban Akhter, Abdulhadi S. Burzangi, Huda Alkreathy, Basma Alharthy, Sabna Kotta, Shadab Md, Md Abdur Rashid, Obaid Afzal, Abdulmalik S. A. Altamimi, and et al. 2022. "Phytosterol-Loaded Surface-Tailored Bioactive-Polymer Nanoparticles for Cancer Treatment: Optimization, In Vitro Cell Viability, Antioxidant Activity, and Stability Studies" Gels 8, no. 4: 219. https://doi.org/10.3390/gels8040219