Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Equipment
2.3. MSMP Production
2.4. Liposome Production
2.5. Physicochemical Characterization of Liposomes
2.6. Transmission Electron Microscopy (TEM)
2.7. Oxaliplatin Encapsulation Efficiency
2.8. HPLC Analysis and Validation
2.9. Cell Cultures
2.10. MTT Assay
2.11. Cellular Uptake of Liposomes
2.12. Surface Charge Modification of MSMP
2.13. MSV Assembly
2.14. Release Kinetics of Liposomes from MSV
2.15. Size of Released Liposomes
2.16. Confocal Microscopy of Cells Incubated with MSVs.
3. Results
3.1. Design of Particles
3.2. Effect of Liposomal Formulations in Cell Cultures
3.3. Multistage Vector Assembly
3.4. Release of Liposomes from the Multistage Vector
3.5. Effects of the Multistage Vector in Cell Culture
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Form. | Composition | Short Name | Procedure | Tm | Dh | PDI | ZP |
---|---|---|---|---|---|---|---|
1 | DOPC/DSPEmPEG2000 (7/3 molar ratio) | – | Extrusion 50 nm/Sonication | 37 °C | 58.96 ± 1.21 | 0.369 ± 0.02 | −0.57 ± 0.03 |
2 | PC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 50 nm/Sonication | 45 °C | 55.20 ± 2.25 | 0.363 ± 0.09 | −1.59 ± 0.20 |
3 | DOPC/DSPEmPEG2000 (7/5 molar ratio) | – | Extrusion 50 nm/Sonication | 45 °C | 55.5 ± 2.1 | 0.340 ± 0.03 | −2.15 ± 0.30 |
4 | DOPC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 50 nm/Sonication | 37 °C | 45.33 ± 1.2 | 0.476 ± 0.12 | 0.858 ± 0.10 |
5 | PC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 50 nm/Sonication | 45 °C | 52.95 ± 2.1 | 0.467 ± 0.10 | −1.59 ± 0.20 |
6 | PC/DSPEmPEG2000 (7/5 molar ratio) | – | Extrusion 50 nm/Sonication | 45 °C | 53.46 ± 2.10 | 0.377 ± 0.09 | −4.83 ± 1.10 |
7 | DOPC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 50 nm/Sonication | 37 °C | 45.22 ± 1.90 | 0.471 ± 0.12 | −6.87 ± 1.30 |
8 | PC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 50 nm/Sonication | 45 °C | 53.03 ± 0.90 | 0.491 ± 0.13 | −8.72 ± 0.90 |
9 | PC/DSPEmPEG2000 (7/5 molar ratio) | – | Extrusion 30 nm | 45 °C | 52.93 ± 1.25 | 0.271 ± 0.12 | −9.47 ± 1.70 |
10 | PC/DSPEmPEG2000 (7/6 molar ratio) | – | Extrusion 30 nm | 45 °C | 47.76 ± 3.90 | 0.273 ± 0.09 | −15.0 ± 2.10 |
11 | DPPC/Chol/PE/DSPEmPEG2000 (7/7/4/1 molar ratio) | – | Extrusion 50 nm/Sonication | 50 °C | 55.58 ± 1.90 | 0.194 ± 0.09 | −12.63 ± 1.23 |
12 | PC/Chol/PE/DSPEmPEG2000 (7/7/4/1 molar ratio) | – | Extrusion 50 nm/Sonication | 50 °C | 54.16 ± 2.10 | 0.197 ± 0.08 | −11.06 ± 0.30 |
13 | DOPC/DPPC/DSPEmPEG2000 (7/4/3 molar ratio) | – | Extrusion 50 nm/30 nm | 40 °C | 51.5 ± 8.90 | 0.172 ± 0.10 | −5.40 ± 5.0 |
14 | DPPC/DPPS/Chol (7/4/7 molar ratio) | – | Extrusion 50 nm | 50 °C | 64.93 ± 1.21 | 0.053 ± 0.02 | −41.94 ± 2.90 |
15 | DSPC/DSPEmPEG2000 (7/3 molar ratio) | DS | Extrusion 30 nm | 60 °C | 26.3 ± 1.2 | 0.578 ± 0.02 | −10.51 ± 0.18 |
16 | DSPC/DOPC/DSPEmPEG2000 (7/1/2 molar ratio) | DO | Extrusion 30 nm | 60 °C | 54.46 ± 3.03 | 0.209 ± 0.03 | −9.84 ± 0.40 |
4 oxa | DOPC/DSPEmPEG2000 (7/6 molar ratio) + oxa | – | Extrusion 30 nm | 42 °C | 64.5 ± 1.1 | 0.239 ± 0.91 | −6.17 ± 1.23 |
10 oxa | PC/DSPEmPEG2000 (7/6 molar ratio) + oxa | – | Extrusion 30 nm | 50 °C | 75.2 ± 1.2 | 0.365 ± 0.14 | −4.25 ± 1.60 |
13 oxa | DOPC/DPPC/DSPEmPEG2000 (7/4/3 molar ratio) + oxa | – | Extrusion 30 nm | 50 °C | 64.65 ± 5.15 | 0.098 ± 0.01 | −5.35 ± 2.40 |
15 oxa | DSPC/DSPEmPEG2000 (7/3 molar ratio) + oxa | DS-oxa | Extrusion 30 nm | 60 °C | 44.25 ± 4.25 | 0.315 ± 0.04 | −10.95 ± 0.4 |
16 oxa | DSPC/DOPC/DSPEmPEG2000 (7/1/2 molar ratio) + oxa | DO-oxa | Extrusion 30 nm | 60 °C | 42.60 ± 3.80 | 0.251 ± 0.01 | −9.41 ± 1.95 |
IC50 | |||
---|---|---|---|
Time (h) | Free oxa | DO-oxa | DS-oxa |
24 | 1.9 ± 0.7 μM | N.A. | N.A. |
48 | 1.3 ± 0.6 μM | 1.6 ± 0.6 μM | 2.2 ± 0.8 μM |
72 | 0.8 ± 0.3 μM | 1.6 ± 0.7 μM | 1.9 ± 0.8 μM |
Time (h) | Treatment | IC50 (μM) | SD (μM) |
---|---|---|---|
48 | Free oxa | 1.3 | ± 0.2 |
MSV DO-oxa | 1.2 | ±0.1 | |
MSV DS-oxa | 1.5 | ±0.3 | |
72 | Free oxa | 0.7 | ±0.1 |
MSV DO-oxa | 1.0 | ±0.1 | |
MSV DS-oxa | 1.5 | ±0.3 |
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Cevenini, A.; Celia, C.; Orrù, S.; Sarnataro, D.; Raia, M.; Mollo, V.; Locatelli, M.; Imperlini, E.; Peluso, N.; Peltrini, R.; et al. Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy. Pharmaceutics 2020, 12, 559. https://doi.org/10.3390/pharmaceutics12060559
Cevenini A, Celia C, Orrù S, Sarnataro D, Raia M, Mollo V, Locatelli M, Imperlini E, Peluso N, Peltrini R, et al. Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy. Pharmaceutics. 2020; 12(6):559. https://doi.org/10.3390/pharmaceutics12060559
Chicago/Turabian StyleCevenini, Armando, Christian Celia, Stefania Orrù, Daniela Sarnataro, Maddalena Raia, Valentina Mollo, Marcello Locatelli, Esther Imperlini, Nicoletta Peluso, Rosa Peltrini, and et al. 2020. "Liposome-Embedding Silicon Microparticle for Oxaliplatin Delivery in Tumor Chemotherapy" Pharmaceutics 12, no. 6: 559. https://doi.org/10.3390/pharmaceutics12060559