Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Preparation of DDS
2.2.1. Preparation of MS
2.2.2. Preparation of Micelles
2.3. Characterization of DDS
2.3.1. Microscopic Evaluation
2.3.2. FTIR Analysis
2.3.3. NMR Analysis
2.3.4. HPLC Measurements
2.4. Encapsulation Efficiency
2.5. In Vitro Release Studies
2.5.1. Drug Release from MS
2.5.2. Drug Release from Micelles
2.6. In Vitro Cytotoxicity Studies
2.7. Statistical Analysis
3. Results
3.1. Characteristics of DDS
3.2. In Vitro Drug Release
3.3. FTIR Analysis
3.4. Cytotoxic Activity of EpoB and Rap
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Name of DDS | Composition of DDS | |
---|---|---|
Amount of PLA (%) | Amount of PLA–PEG (%) | |
Microspheres | ||
PLA 100/PLA–PEG 0 | 100 | 0 |
PLA 75/PLA–PEG 25 | 75 | 25 |
PLA 50/PLA–PEG 50 | 50 | 50 |
PLA 25/PLA–PEG 75 | 25 | 75 |
PLA 0/PLA–PEG 100 | 0 | 100 |
Micelles | ||
Micelles | 0 | 100 |
Name of DDS | EE of EpoB (%) | EE of Rap (%) |
---|---|---|
PLA 100/PLA–PEG 0 + EpoB | 8.9 ± 1.2 | - |
PLA 100/PLA–PEG 0 + Rap | - | 83.0 ± 4.2 |
PLA 100/PLA–PEG 0 + EpoB and Rap | 13.1 ± 2.3 | 48.1 ± 1.5 |
PLA 75/PLA–PEG 25 + EpoB | 7.2 ± 2.3 | - |
PLA 75/PLA–PEG 25 + Rap | - | 96.0 ± 3.7 |
PLA 75/PLA–PEG 25 + EpoB and Rap | 9.4 ± 1.9 | 54.2 ± 0.9 |
PLA 50/PLA–PEG 50 + EpoB | 2.9 ± 0.2 | |
PLA 50/PLA–PEG 50 + Rap | - | 95.0 ± 4.7 |
PLA 50/PLA–PEG 50 + EpoB and Rap | 4.2 ± 1.2 | 59.7 ± 1.3 |
PLA 25/PLA–PEG 75 + EpoB | 6.8 ± 3.6 | - |
PLA 25/PLA–PEG 75 + Rap | - | 91.0 ± 8.9 |
PLA 25/PLA–PEG 75 + EpoB and Rap | 7.2 ± 2.7 | 53.9 ± 1.8 |
Micelles + EpoB | 43.8 ± 3.8 | |
Micelles + Rap | - | 96.5 ± 3.3 |
Micelles + EpoB and Rap | 41.0 ± 3.8 | 40.3 ± 0.7 |
Name of DDS | Korsmeyer-Peppas (R2) | Peppas-Sahlin (R2) | ||
---|---|---|---|---|
EpoB | Rap | EpoB | Rap | |
PLA 100/PLA–PEG 0 + EpoB | 0.945 | - | 0.952 | - |
PLA 100/PLA–PEG 0 + Rap | - | 0.951 | - | 0.960 |
PLA 100/PLA–PEG 0 + EpoB and Rap | 0.995 | 0.975 | 0.995 | 0.975 |
PLA 75/PLA–PEG 25 + EpoB | 0.977 | - | 0.992 | - |
PLA 75/PLA–PEG 25 + Rap | - | 0.976 | - | 0.985 |
PLA 75/PLA–PEG 25 + EpoB and Rap | 0.924 | 0.909 | 0.988 | 0.971 |
PLA 50/PLA–PEG 50 + EpoB | 0.972 | - | 0.985 | - |
PLA 50/PLA–PEG 50 + Rap | - | 0.969 | - | 0.982 |
PLA 50/PLA–PEG 50 + EpoB and Rap | 0.972 | 0.876 | 0.992 | 0.961 |
PLA 25/PLA–PEG 75 + EpoB | 0.999 | - | 0.999 | - |
PLA 25/PLA–PEG 75 + Rap | - | 0.996 | - | 0.997 |
PLA 25/PLA–PEG 75 + EpoB and Rap | 0.968 | 0.925 | 0.977 | 0.982 |
Micelles + EpoB | 0.956 | - | 0.996 | - |
Micelles + Rap | - | 0.919 | - | 0.988 |
Micelles + EpoB and Rap | 0.966 | 0.982 | 0.976 | 0.982 |
PLA–PEG | Rap | EpoB | Assignment |
---|---|---|---|
3500 | 3588 3577 sh 3419 | 3497 3395 | Overtonevν OH |
3000–2700 | 3000–2700 | 3000–2700 | ν CH, CH2 |
1754 | ν C=O ester PLA | ||
1720 1645 1634 | 1746 1742 sh 1686 | ν C=O ester free ν C=O ester bonded ν C=O ketone ν C=O amide (I amide bands) |
Drugs Concentration | Free Drugs | Micelles PLA100/PLA–PEG0 | Microspheres PLA100/PLA–PEG0 | Microspheres PLA50/PLA–PEG50 |
---|---|---|---|---|
Control (blank) | 100.00 ± 0.44 | 100.00 ± 0.29 | 100.00 ± 0.45 | 100.00 ± 0.24 |
EpoB 10 nM | 24.67 ± 1.11 * | 18.77 ± 1.23 * | 100.25 ± 0.54 | 19.58 ± 1.32 * |
Rap 4 nM | 99.22 ± 1.42 | 98.89 ± 1.72 | 98.42 ± 0.51 | 97.63 ± 1.22 |
EpoB 10 nM + Rap 4 nM | 19.52 ± 1.23 * | 14.18 ± 1.75 * | 97.29 ± 0.97 | 16.25 ± 1.39 * |
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Jelonek, K.; Zajdel, A.; Wilczok, A.; Kaczmarczyk, B.; Musiał-Kulik, M.; Hercog, A.; Foryś, A.; Pastusiak, M.; Kasperczyk, J. Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells. Pharmaceutics 2021, 13, 1881. https://doi.org/10.3390/pharmaceutics13111881
Jelonek K, Zajdel A, Wilczok A, Kaczmarczyk B, Musiał-Kulik M, Hercog A, Foryś A, Pastusiak M, Kasperczyk J. Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells. Pharmaceutics. 2021; 13(11):1881. https://doi.org/10.3390/pharmaceutics13111881
Chicago/Turabian StyleJelonek, Katarzyna, Alicja Zajdel, Adam Wilczok, Bożena Kaczmarczyk, Monika Musiał-Kulik, Anna Hercog, Aleksander Foryś, Małgorzata Pastusiak, and Janusz Kasperczyk. 2021. "Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells" Pharmaceutics 13, no. 11: 1881. https://doi.org/10.3390/pharmaceutics13111881
APA StyleJelonek, K., Zajdel, A., Wilczok, A., Kaczmarczyk, B., Musiał-Kulik, M., Hercog, A., Foryś, A., Pastusiak, M., & Kasperczyk, J. (2021). Comparison of PLA-Based Micelles and Microspheres as Carriers of Epothilone B and Rapamycin. The Effect of Delivery System and Polymer Composition on Drug Release and Cytotoxicity against MDA-MB-231 Breast Cancer Cells. Pharmaceutics, 13(11), 1881. https://doi.org/10.3390/pharmaceutics13111881