In vivo evaluation of microspheres containing the angiogenesis inhibitor, TNP-470, and the metastasis suppression with liver metastatic model implanted neuroblastoma.
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+/-0.13g, 1.28+/-0.10g, and 2.54+/-0.97g, 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.
Yasuda
Chikao
C
Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka 589-8511, Japan.
Sakata
Shoei
S
Kakinoki
Sachiro
S
Takeyama
Yoshifumi
Y
Ohyanagi
Harumasa
H
Shiozaki
Hitoshi
H