Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application
Abstract
:1. Introduction
2. Materials and Methods
2.1. Synthesis of BisMH, DTME, and DseME Cross-Linkers
2.2. Synthesis of PEO2k-b-PFMA1.5k
2.3. Critical Micelle Concentration (CMC) Measurement
2.4. The Stability of Non-CCL/DOX and C–C/S–S/Se–Se CCL/DOX Micelles
2.5. Synthesis of DOX-Loaded C–C/S–S/Se–Se CCL Micelles of PEO2k-b-PFMA1.5k via DA Reaction
2.6. In Vitro Release Study of DOX from S–S/Se–Se CCL Micelles
3. Results and Discussion
3.1. Synthesis and Characterization of C–C/S–S/Se–Se CCL Micelles
3.2. Stability of C–C/S–S/Se–Se CCL/DOX and Non-CCL/DOX Micelles
3.3. Drug Loading Studies
3.4. Redox-Responsive Properties of CCL Micelles
3.5. Redox-Triggered In Vitro DOX Release
3.6. Cytotoxicity of DOX-Loaded C–C/S–S/Se–Se CCL Micelles and Non-CCL Micelles
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Run | Polymer | Mn (NMR) a (g/mol) | Mn (GPC) b (g/mol) | Ð |
---|---|---|---|---|
1 | PEO2k-Br | 2150 | 2300 | 1.06 |
2 | PEO2k-b-PFMA1.5k | 3645 | 3900 | 1.12 |
Micelles | Blank Micelles | DOX-Loaded Micelles b | ||||
---|---|---|---|---|---|---|
Diameter a (nm) | PDI a | Diameter a (nm) | PDI a | LC (%) | LE (%) | |
Non-CCL | 155 ± 35 | 0.243 | 164 ± 54 | 0.261 | 60.28 | 6.85 |
C-C/CCL | 124 ± 35 | 0.243 | 147 ± 53 | 0.237 | 68.36 | 7.76 |
S-S/CCL | 133 ± 31 | 0.263 | 152 ± 55 | 0.260 | 74.45 | 8.45 |
Se-Se/CCL | 139 ± 31 | 0.295 | 149 ± 54 | 0.251 | 79.50 | 9.03 |
Micelles | Time (h) | 5 mM GSH a | 50 mM H2O2 a | ||
---|---|---|---|---|---|
Diameter (nm) | PDI | Diameter (nm) | PDI | ||
C-C/CCL | 24 | 124 ± 54 | 0.253 | 127 ± 54 | 0.277 |
S-S/CCL | 24 | 141 ± 70 | 0.240 | 135 ± 31 | 0.293 |
Se-Se/CCL | 24 | 156 ± 65 | 0.255 | 161 ± 54 | 0.327 |
Micelles | 10 mM GSH a | 100 mM H2O2 a | |||
Diameter (nm) | PDI | Diameter (nm) | PDI | ||
C-C/CCL | 0 | 124 ± 35 | 0.243 | -- | -- |
12 | 121 ± 57 | 0.248 | 125 ± 53 | 0.236 | |
24 | 126 ± 52 | 0.232 | 130 ± 52 | 0.211 | |
S-S/CCL | 0 | 133 ± 31 | 0.263 | -- | -- |
12 | 148 ± 56 | 0.271 | 134 ± 64 | 0.271 | |
24 | 150 ± 75 | 0.355 | 137 ± 62 | 0.275 | |
Se-Se/CCL | 0 | 139 ± 31 | 0.295 | -- | -- |
12 | 155 ± 61 | 0.293 | 159 ± 55 | 0.298 | |
24 | 158 ± 88 | 0.388 | 164 ± 69 | 0.322 |
Code | GSH/H2O2 | pH | Zero-Order | First Order | Higuchi Model | Korsmeyer-Peppas | ||||
---|---|---|---|---|---|---|---|---|---|---|
K0 | r2 | K1 | r2 | KH | r2 | n | r2 | |||
Non-CCL/DOX | NA | 7.4 | 0.932 | 1.558 | 0.013 | 1.036 | 5.966 | 0.475 | 0.403 | 0.959 |
5.0 | 1.881 | 0.032 | 0.046 | 0.719 | 11.470 | 0.886 | 0.525 | 0.981 | ||
S-S/DOX | NA | 7.4 | 0.160 | 0.206 | 0.002 | 0.239 | 0.964 | 0.895 | 0.548 | 0.884 |
5.0 | 0.522 | 0.163 | 0.006 | 0.012 | 3.227 | 0.822 | 0.595 | 0.980 | ||
Se-Se/DOX | NA | 7.4 | 0.239 | 0.648 | 0.003 | 0.568 | 1.497 | 0.734 | 0.476 | 0.955 |
5.0 | 0.608 | 0.692 | 0.007 | 0.473 | 3.851 | 0.645 | 0.550 | 0.938 | ||
S-S/DOX | 10 mM GSH | 7.4 | 0.952 | 0.090 | 0.013 | 0.202 | 5.839 | 0.853 | 0.493 | 0.933 |
5.0 | 1.739 | 0.063 | 0.039 | 0.672 | 10.618 | 0.871 | 0.631 | 0.997 | ||
Se-Se/DOX | 10 mM GSH | 7.4 | 1.173 | 0.426 | 0.018 | 0.049 | 7.270 | 0.809 | 0.432 | 0.994 |
5.0 | 1.975 | 0.107 | 0.056 | 0.730 | 12.201 | 0.820 | 0.650 | 0.996 | ||
S-S/DOX | 100 mM H2O2 | 7.4 | 0.255 | 1.031 | 0.003 | 0.933 | 1.622 | 0.590 | 0.515 | 0.994 |
5.0 | 0.709 | 0.383 | 0.009 | 0.155 | 4.451 | 0.723 | 0.608 | 0.947 | ||
Se-Se/DOX | 100 mM H2O2 | 7.4 | 1.466 | 0.326 | 0.028 | 0.284 | 9.152 | 0.770 | 0.605 | 0.992 |
5.0 | 2.026 | 0.049 | 0.056 | 0.805 | 12.380 | 0.869 | 0.620 | 0.993 |
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Yadav, S.; Ramesh, K.; Reddy, O.S.; Karthika, V.; Kumar, P.; Jo, S.-H.; Yoo, S.I.; Park, S.-H.; Lim, K.T. Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application. Pharmaceutics 2023, 15, 1159. https://doi.org/10.3390/pharmaceutics15041159
Yadav S, Ramesh K, Reddy OS, Karthika V, Kumar P, Jo S-H, Yoo SI, Park S-H, Lim KT. Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application. Pharmaceutics. 2023; 15(4):1159. https://doi.org/10.3390/pharmaceutics15041159
Chicago/Turabian StyleYadav, Sonyabapu, Kalyan Ramesh, Obireddy Sreekanth Reddy, Viswanathan Karthika, Parveen Kumar, Sung-Han Jo, Seong II Yoo, Sang-Hyug Park, and Kwon Taek Lim. 2023. "Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application" Pharmaceutics 15, no. 4: 1159. https://doi.org/10.3390/pharmaceutics15041159
APA StyleYadav, S., Ramesh, K., Reddy, O. S., Karthika, V., Kumar, P., Jo, S.-H., Yoo, S. I., Park, S.-H., & Lim, K. T. (2023). Redox-Responsive Comparison of Diselenide and Disulfide Core-Cross-Linked Micelles for Drug Delivery Application. Pharmaceutics, 15(4), 1159. https://doi.org/10.3390/pharmaceutics15041159