Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Biocatalytic Synthesis and Characterisation of the ε-Caprolactone-12-hydroxystearic Acid Copolymer
2.3. Preparation of Nanoparticles by Double Emulsion Solvent Evaporation Method
2.4. Characterisation of Nanoparticles
2.4.1. Particle Size, Morphology and Zeta Potential Analysis
2.4.2. Yield and Encapsulation Efficiency
2.4.3. Quantification of BSA by Micro Bicinchoninic Acid Protein Assay
2.4.4. In Vitro Drug Release
2.4.5. In Vitro Cytotoxicity Study
2.4.6. Data Processing
3. Results and Discussion
3.1. Encapsulation of the Active Agents using BSA as Additive
3.2. Simultaneous Encapsulation of Sorafenib and Cisplatin using iRGD
3.3. Drug Release Study
3.4. Cytotoxicity Test
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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Sample | o/w Ratio | Polymer [%] | PVA [%] | BSA [mg] | EDC [mg] | Z-avg [nm] | PDI |
---|---|---|---|---|---|---|---|
12CLBSA1 | 1/2 | 1 | 0.5 | 1 | 0 | 476.6 ± 9.3 | 0.450 ± 0.018 |
12CLBSA2 | 1/3 | 1 | 1 | 1 | 0 | 241.3 ± 5.8 | 0.341 ± 0.004 |
12CLBSA3 | 1/3 | 2 | 1 | 1 | 0 | 481.9 ± 39.6 | 0.692 ± 0.022 |
12CLBSA4 | 1/3 | 1 | 1 | 0.5 | 0 | 232.3 ± 10.2 | 0.360 ± 0.051 |
12CLBSA5 | 1/5 | 1 | 1 | 1 | 0 | 269.9 ± 7.8 | 0.355 ± 0.019 |
12CLBSA6 | 1/5 | 1 | 1 | 0.5 | 0 | 245.5 ± 3.1 | 0.275 ± 0.007 |
12CLBSA7 | 1/4 | 1 | 1 | 1 | 0 | 301.2 ± 7.6 | 0.461 ± 0.018 |
12CLBSA8 | 1/4 | 1 | 1 | 0.5 | 0 | 338.8 ± 11.6 | 0.568 ± 0.035 |
12CLBSA9 | 1/5 | 1 | 1 | 1 | 1 | 438.5 ± 25.1 | 0.810 ± 0.121 |
12CLBSA10 | 1/5 | 1 | 1 | 0.5 | 1 | 250.7 ± 8.3 | 0.353 ± 0.038 |
12CLBlank | 1/5 | 1 | 1 | 0 | 0 | 215.2 ± 1.4 | 0.222 ± 0.011 |
Sample | Sorafenib [mg] | Cisplatin [mg] | EDC [mg] | Z-avg [nm] | PDI |
---|---|---|---|---|---|
12CLBSASOR1 | 1 | 0 | 0 | 223.4 ± 2.4 | 0.243 ± 0.008 |
12CLBSASOR2 a | 1 | 0 | 1 | 274.4 ± 8.6 | 0.582 ± 0.018 |
12CLBSASOR3 b | 1 | 0 | 1 | 212.3 ± 0.8 | 0.258 ± 0.028 |
12CLBSASORCIS1 | 0.5 | 0.5 | 0 | 239.6 ± 3.7 | 0.378 ± 0.014 |
12CLBSASORCIS2 a | 0.5 | 0.5 | 1 | 196.1 ± 1.7 | 0.081 ± 0.013 |
12CLBSASORCIS3 b | 0.5 | 0.5 | 1 | 249.3 ± 8.1 | 0.362 ± 0.021 |
12CLBSACIS1 | 0 | 1 | 0 | 252.2 ± 15.0 | 0.413 ± 0.02 |
12CLBSACIS2 a | 0 | 1 | 1 | 246.3 ± 27.2 | 0.397 ± 0.070 |
12CLBSACIS3 b | 0 | 1 | 1 | 188.9 ± 2.0 | 0.091 ± 0.008 |
Sample | BSA [mg] | DCC [mg] | Z-avg [nm] | PDI | EE BSA [%] | Yield [%] |
---|---|---|---|---|---|---|
12CLBSADCC1 | 0.5 | 1 | 217.6 ± 2.0 | 0.129 ± 0.014 | 71 | - |
12CLBSADCC2 | 0.5 | 2 | 225.9 ± 2.2 | 0.115 ± 0.015 | 73 | 46 |
12CLBSADCC3 | 1 | 2 | 219.7 ± 1.7 | 0.121 ± 0.011 | 82 | 46 |
12CLBSADCCBlank | 0 | 2 | 233.4 ± 1.4 | 0.136 ± 0.020 | - | 47 |
Sample | Cisplatin [mg] | DCC [mg] | Z-avg [nm] | PDI | Yield [%] | EE Cisplatin [%] |
---|---|---|---|---|---|---|
12CLBSACISH4 | 0.5 | - | 204.6 ± 1.1 | 0.250 ± 0.014 | 40 | 24 |
12CLBSACISH5 Blank | - | 2 | 212.9 ± 2.4 | 0.171 ± 0.019 | 39 | - |
12CLBSACISH5 | 0.5 | 2 | 209.8 ± 3.0 | 0.209 ± 0.015 | 61 | 28 |
Sample | iRGD [mg] | Z-avg [nm] | PDI | Zeta Potential [mV] | Yield [%] |
---|---|---|---|---|---|
DCCRGD Blank | - | 210.8 ± 1.6 | 0.119 ± 0.019 | −11.00 | 59 |
DCCRGD1 | 0.5 | 223.7 ± 3.0 | 0.143 ± 0.03 | −11.20 | 49 |
DCCRGD2 | 1 | 218.1 ± 0.9 | 0.158 ± 0.014 | −11.80 | 59 |
Sample | Z-avg [nm] | PDI | Zeta Potential [mV] | Yield [%] | EE Sorafenib [%] | EE Cisplatin [%] | EE iRGD [%] |
---|---|---|---|---|---|---|---|
iRGDBlank | 220.6 ± 4.2 | 0.256 ± 0.016 | −9.42 | 63 ± 12 | - | - | - |
SORiRGDCIS | 220.8 ± 2.5 | 0.221 ± 0.021 | −10.0 | 65 ± 11 | 54 ± 1.0 | 25 ± 1.0 | 42 ± 3.0 |
DCCSOR-iRGDCIS | 205.9 ± 2.8 | 0.148 ± 0.012 | −11.8 | 74 ±13 | 55 ± 2.8 | 23 ± 2.1 | 29 ± 3.1 |
Concentration Group | Normality Test (Shapiro–Wilk) | Homoscedasticity (Bartlett Test) | One-way-ANOVA/Kruskal–Wallis | Post-hoc (Tukey HSD/Nemenyi or Dunn) |
---|---|---|---|---|
2.5 µg/mL | C: p = 0.440 S: p = 0.630 CS: p = 0.694 | p = 0.219 | F = 7.922, df = 2, p < 0.01 ** | C-CS: p < 0.01 ** |
5.0 µg/mL | C: p = 0.296 S: p = 0.374 CS: p = 0.027 | p = 0.158 | Chi-sq = 13.03, df = 2, p < 0.01 ** | C-CS: p < 0.01 ** S-CS: p < 0.05 * |
12.5 µg/mL | C: p = 0.041 S: p = 0.307 CS: p = 0.350 | p = 0.466 | Chi-sq = 14.25, df = 2, p < 0.001 *** | C-CS: p < 0.01 ** S-CS: p < 0.01 ** |
25.0 µg/mL | C: p = 0.048 S: p = 0.227 CS: p = 0.829 | p = 0.321 | Chi-sq = 18.12, df = 2, p < 0.001 *** | C-S: p < 0.05 * C-CS: p < 0.001 *** |
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Kántor, I.; Dreavă, D.; Todea, A.; Péter, F.; May, Z.; Biró, E.; Babos, G.; Feczkó, T. Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer. Biomedicines 2022, 10, 43. https://doi.org/10.3390/biomedicines10010043
Kántor I, Dreavă D, Todea A, Péter F, May Z, Biró E, Babos G, Feczkó T. Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer. Biomedicines. 2022; 10(1):43. https://doi.org/10.3390/biomedicines10010043
Chicago/Turabian StyleKántor, Izolda, Diana Dreavă, Anamaria Todea, Francisc Péter, Zoltán May, Emese Biró, György Babos, and Tivadar Feczkó. 2022. "Co-Entrapment of Sorafenib and Cisplatin Drugs and iRGD Tumour Homing Peptide by Poly[ε-caprolactone-co-(12-hydroxystearate)] Copolymer" Biomedicines 10, no. 1: 43. https://doi.org/10.3390/biomedicines10010043