Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Cell Cultures
2.3. Animals
2.4. Synthesis of FOL-S100
2.5. Preparation of FOL-MTX&CAT Liposomes
2.6. Characterization of Liposomes
2.7. In Vitro Drug Release
2.8. Validation of LPS Activated RAW264.7 Cell Model
2.9. Intracellular Uptake of Liposomes
2.10. In Vitro Cytotoxicity Study
2.11. Pharmacokinetic and In Vivo Biodistribution Studies
2.12. Therapeutic Efficacy of Liposomes in CIA Mice
2.13. Statistical Analysis
3. Results and Discussion
3.1. Characterization of FOL-S100
3.2. Preparation and Characterization of Liposomes
3.3. In Vitro Drug Release
3.4. Intracellular Uptake of Liposomes in LPS Activated RAW 264.7 Cells
3.5. In Vitro Cytotoxicity Study
3.6. Pharmacokinetics and In Vivo Biodistribution
3.7. Therapeutic Efficacy and Safety
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Formulations | Particle Size (nm) | PDI a | Zeta Potential (mV) | EE (%) b | DL (%) c | ||
---|---|---|---|---|---|---|---|
MTX | CAT | MTX | CAT | ||||
MTX-L | 134.9 ± 2.6 | 0.17 ± 0.06 | –8.5 ± 0.9 | 89.24 ± 3.18 | — | 7.18 ± 0.36 | — |
MTX&CAT-L | 141.2 ± 3.2 | 0.18 ± 0.04 | –8.8 ±1.1 | 84.65 ± 3.74 | 76.52 ± 2.62 | 6.75 ± 0.52 | 2.36 ± 0.42 |
FOL-MTX&CAT-L | 145.5 ± 4.5 | 0.17 ± 0.03 | –4.2 ± 0.8 | 86.72 ± 2.54 | 79.44 ± 1.85 | 6.94 ± 0.72 | 2.52 ± 0.26 |
Parameters | MTX-S | MTX-L | MTX&CAT-L | FOL-MTX&CAT-L |
---|---|---|---|---|
AUC0-24 (h⋅μg/mL) | 4.91 ± 0.08 | 78.86 ± 2.84 ** | 80.13 ± 4.52 ** | 82.22 ± 6.74 ** |
T1/2 (h) | 1.23 ± 0.02 | 8.52 ± 0.82 ** | 9.16 ± 1.19 ** | 9.40 ± 2.06 ** |
MRT (h) | 1.85 ± 0.06 | 11.96 ± 2.86 ** | 12.85 ± 3.63 ** | 13.08 ± 2.65 ** |
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Chen, M.; Daddy J.C., K.A.; Su, Z.; Guissi, N.E.I.; Xiao, Y.; Zong, L.; Ping, Q. Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis. Pharmaceutics 2019, 11, 582. https://doi.org/10.3390/pharmaceutics11110582
Chen M, Daddy J.C. KA, Su Z, Guissi NEI, Xiao Y, Zong L, Ping Q. Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis. Pharmaceutics. 2019; 11(11):582. https://doi.org/10.3390/pharmaceutics11110582
Chicago/Turabian StyleChen, Minglei, Kambere Amerigos Daddy J.C., Zhigui Su, Nida El Islem Guissi, Yanyu Xiao, Li Zong, and Qineng Ping. 2019. "Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis" Pharmaceutics 11, no. 11: 582. https://doi.org/10.3390/pharmaceutics11110582