In vivo evaluation of microspheres containing the angiogenesis inhibitor,TNP-470, and the metastasis suppression with liver metastatic model implanted neuroblastoma |
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| Authors: | Chikao Yasuda Shoei Sakata Sachiro Kakinoki Yoshifumi Takeyama Harumasa Ohyanagi Hitoshi Shiozaki |
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| Institution: | 1. Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan;2. Interdisciplinary Graduate School of Science and Technology, Kinki University, Osaka, Japan;1. National Institute of Polar Research (NIPR), 10-3 Midori-cho, Tachikawa, Tokyo 190-8518, Japan;2. Department of Polar Science, SOKENDAI (The Graduate University for Advanced Studies), 10-3 Midori-cho, Tachikawa, Tokyo 190-8518, Japan;3. Research Institute for Sustainable Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), 3-11-32 Kagamiyama, Higashihiroshima, Hiroshima 739-0046, Japan;1. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903, Ribeirão Preto, SP, Brazil;2. Universidade de Sorocaba (Uniso)—Rodovia Raposo Tavares km 92,5, São Paulo, Brazil;3. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, 09210-580, Santo André, SP, Brazil |
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| Abstract: | TNP-470 (AGM-1470, O-(chloroacetylcarbamoyl) fumagillol), which strongly inhibits the angiogenesis, is promising as a new drug for tumor dormancy therapy; however, TNP-470 is very unstable in vitro and in vivo. We previously prepared TNP-470 containing microspheres composed of poly (lactic acid) with medium-chain triglyceride, and demonstrated that the microspheres released TNP-470 over the long-term in vitro. The present study was undertaken to evaluate the release profile of TNP-470 in vivo and the inhibitory effect on hepatic metastasis of neuroblastoma. It was found that the microspheres could maintain high levels of TNP-470 in the blood plasma for over 4 weeks in vivo. In addition, hepatic metastasis of neuroblastoma was strongly inhibited at 2 weeks after intraperitoneal injection of the microspheres. Following 2 weeks of treatment, the liver weights of mice injected with TNP-DDS (TNP-DDS (H), and TNP-DDS (L) groups) and those injected with only physiological saline (C-1300 group) after implantation of neuroblastoma cells were 1.18 ± 0.13 g, 1.28 ± 0.10 g, and 2.54 ± 0.97 g, respectively (p < 0.05; C-1300 group compared with the TNP-DDS (H) and the TNP-DDS (L) groups, respectively). It was evident that microspheres containing TNP-470 have an excellent potential for clinical application in tumor dormancy therapy. |
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