pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers
Abstract
:1. Introduction
2. Results and Discussion
2.1. Microwave Synthesis of Poly(ethylene glycol)lactate
2.2. Synthesis of Poly[poly(ethylene glycol) H-phosphonate]-b-[poly(ethylene glycol)lactate H-phosphonate]
2.3. One-Pot Synthesis of Poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethyleneglycol)lactate phosphate]s
One-Pot Synthesis of Poly[hexadecylpoly(ethylene glycol) phosphate)-b-hexadecyl-poly(ethylene glycol)lactate phosphate]
2.4. Self-Assembly of Poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate]s and Particle Size Distribution and Drug Loading and Encapsulation Efficiency for Doxorubicin
2.4.1. Particle Size Distribution
2.4.2. Drug Loading and Encapsulation Efficiency for Doxorubicin
2.5. Release Rate of Loaded Doxorubicin from Micelles
2.6. Cytotoxicity Test
2.7. Cell Uptake Test Using Confocal Laser Microscopy (CLSM)
2.8. Cell Uptake Test Using Flow Cytometry (FACS)
2.9. Pharmacokinetics Test Using Prepared Micelles
2.10. Comparative Analysis
3. Materials and Methods
3.1. Materials
3.2. Characterization Methods and Instruments
3.3. Microwave Synthesis of Poly(ethylene glycol)lactate
3.4. Synthesis of Poly[poly(ethylene glycol) H-phosphonate]-b-[poly(ethylene glycol)lactate H-phosphonate]
3.5. Synthesis of Poly[alkylpoly(ethylene glycol) phosphate-b-alkylpoly(ethylene glycol)lactate phosphate]s
3.5.1. Synthesis of Poly[hexadecylpoly(ethylene glycol) phosphate-b-[hexadecylpoly(ethylene glycol)lactate phosphate]
3.5.2. Synthesis of Poly[tetradecylpoly(ethylene glycol) phosphate-b-tetradecylpoly(ethylene glycol)lactate phosphate]
3.5.3. Synthesis of Poly[octadecylpoly(ethylene glycol) phosphate)-b-octadecylpoly(ethylene glycol)lactate phosphate]
3.6. Measurement of Polymeric Micelle Size
3.7. Preparation of Doxorubicin-Loaded Micelles
3.8. Measuring the Drug Loading and Encapsulation Efficiency of Micelles for Doxorubicin
3.9. Evaluation of Release Properties of Doxorubicin-Encapsulated Micelles
3.10. Cytotoxicity Test Using WST-8 Assay
3.11. Cell Uptake Test Using Confocal Laser Microscopy (CLSM)
3.12. Cell Uptake Test Using Flow Cytometry (FACS)
3.13. Pharmacokinetics Study Using Prepared Micelles
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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Polymer | Micelle Size (nm) | DOX-Micelle Size (nm) | Micelle PDI | DOX-Micelle PDI |
---|---|---|---|---|
C14 | 71.0 ± 48.9 | 116.9 ± 53.8 | 0.257 ± 0.02 | 0.230 ± 0.02 |
C16 | 105.3 ± 45.3 | 119.9 ± 47.6 | 0.182 ± 0.01 | 0.200 ± 0.01 |
C18 | 86.4 ± 43.4 | 100.2 ± 41.1 | 0.231 ± 0.02 | 0.240 ± 0.002 |
Polymer | Yield (%) | Drug Loading (%) | Encapsulation Efficiency (%) |
---|---|---|---|
C14 | 78.1 ± 5.9 | 1.5 ± 0.2 | 31.4 ± 2.0 |
C16 | 89.8 ± 8.3 | 3.2 ± 0.3 | 57.4 ± 3.2 |
C18 | 84.2 ± 7.0 | 2.4 ± 0.2 | 52.9 ± 0.1 |
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Mochizuki, K.; Mitova, V.; Makino, K.; Terada, H.; Takeuchi, I.; Troev, K. pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers. Int. J. Mol. Sci. 2024, 25, 4518. https://doi.org/10.3390/ijms25084518
Mochizuki K, Mitova V, Makino K, Terada H, Takeuchi I, Troev K. pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers. International Journal of Molecular Sciences. 2024; 25(8):4518. https://doi.org/10.3390/ijms25084518
Chicago/Turabian StyleMochizuki, Kasumi, Violeta Mitova, Kimiko Makino, Hiroshi Terada, Issei Takeuchi, and Kolio Troev. 2024. "pH-Sensitive Amphiphilic Diblock Polyphosphoesters with Lactate Units: Synthesis and Application as Drug Carriers" International Journal of Molecular Sciences 25, no. 8: 4518. https://doi.org/10.3390/ijms25084518