Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Fabrication of Electrospun PCL Nanofiber Sheets
2.2. Drug Release Profile
2.3. Cell Lines and Reagents
2.4. Animals
2.5. Treatment of Subcutaneous Tumor Models
2.6. Peritoneal Metastasis Tumor Therapy in Mice
2.7. Histological Examination
2.8. Quantification of the Serum Lenvatinib Levels
2.9. Statistical Analysis
3. Results
3.1. PCL Nanofiber Sheets Release Lenvatinib in a Sustainable Manner
3.2. Nanofibrous Sheets Incorporating Lenvatinib Exhibited Antitumor Effects
3.3. Histopathological Analysis
3.4. Lenvatinib Sheets Maintain the Serum Drug Level
3.5. The Antitumor Effect of Lenvatinib Sheets in Different Insertion Positions
3.6. Lenvatinib Sheets Improved Survival in a Mouse Peritoneal Seeding Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AE | Adverse effects |
DDS | Drug delivery system |
H&E | Hematoxylin and eosin |
HCC | Hepatocellular carcinoma |
MI | Mitotic index |
MVD | Microvessel density |
PBS | Phosphate-buffered saline |
VEGF | Vascular endothelial growth factor |
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2 Weeks | 4 Weeks | 8 Weeks |
---|---|---|
14.85 ± 0.86% | 19.15 ± 0.73% | 28.02 ± 2.15% |
Tumor Volume (mm3) | Aspartate Transaminase (IU/L) | Lactate Dehydrogenase (IU/L) | ||
---|---|---|---|---|
Day 7 | Day 14 | Day 14 | Day 14 | |
No treatment | 1102 ± 138 | 2049 ± 313 | 182 ± 89 | 1417 ± 864 |
Oral 3 mg | 0787 ± 128 | 0780 ± 111 | 115 ± 20 | 0608 ± 117 |
1 mg sheet | 354 ± 55 | 375 ± 54 | 090 ± 26 | 0441 ± 197 |
2 mg sheet | 344 ± 38 | 315 ± 67 | — | — |
Mitotic Index | Vascular Area Ratio | Microvessel Density (mm2) | Internal Diameter of Vessels (μm) | |
---|---|---|---|---|
No treatment | 4.14 ± 0.63% | 4.10 ± 1.34% | 362 ± 48 | 7.29 ± 1.64 |
Oral 3 mg | 2.88 ± 0.36% | 1.92 ± 0.26% | 336 ± 68 | 3.53 ± 0.47 |
1 mg sheet | 1.96 ± 0.36% | 0.97 ± 0.43% | 243 ± 52 | 3.52 ± 0.60 |
Tumor Volume (mm3) | ||
---|---|---|
Day 7 | Day 14 | |
Control | 1233 ± 333 | 2003 ± 327 |
Direct | 247 ± 61 | 377 ± 41 |
Peripheral | 340 ± 67 | 431 ± 67 |
Contralateral | 256 ± 62 | 397 ± 48 |
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Yoshida, T.; Kaibori, M.; Fujisawa, N.; Ishizuka, M.; Sumiyama, F.; Hatta, M.; Kosaka, H.; Matsui, K.; Suzuki, K.; Akama, T.O.; et al. Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model. Nanomaterials 2022, 12, 1364. https://doi.org/10.3390/nano12081364
Yoshida T, Kaibori M, Fujisawa N, Ishizuka M, Sumiyama F, Hatta M, Kosaka H, Matsui K, Suzuki K, Akama TO, et al. Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model. Nanomaterials. 2022; 12(8):1364. https://doi.org/10.3390/nano12081364
Chicago/Turabian StyleYoshida, Terufumi, Masaki Kaibori, Nanami Fujisawa, Mariko Ishizuka, Fusao Sumiyama, Masahiko Hatta, Hisashi Kosaka, Kosuke Matsui, Kensuke Suzuki, Tomoya O. Akama, and et al. 2022. "Efficacy of Nanofiber Sheets Incorporating Lenvatinib in a Hepatocellular Carcinoma Xenograft Model" Nanomaterials 12, no. 8: 1364. https://doi.org/10.3390/nano12081364