Nishiofuku Hideyuki, Tanaka Toshihiro, Fukuoka Yasushi, Sato Takeshi, Masada Tetsuya, Tatsumoto Shota, Sho Masayuki, Yamato Ichiro, Yasuda Satoshi, Matsushima Shigeru, Takano Masato, Ohbayashi Chiho, Kichikawa Kimihiko
Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
J Vasc Interv Radiol. 2017 Mar;28(3):457-464. doi: 10.1016/j.jvir.2016.10.032. Epub 2016 Dec 29.
To evaluate the pharmacokinetics of intraarterial (IA) administration of micellar nanoparticles incorporating SN-38 injection compared with intravenous (IV) administration in a rabbit liver tumor model.
In this animal care committee-approved study, 18 rabbits (mean weight, 3.89 kg; range, 3.20-4.70 kg) with VX2 liver tumors were divided into two groups (IA and IV). Micellar nanoparticles incorporating SN-38 (30 mg/kg) were injected through the left hepatic artery in the IA group and the right femoral vein in the IV group. NK012 and free SN-38 in the plasma, liver parenchyma, and tumors were measured within 24 hours. Histologic examinations were conducted at 2 and 24 hours.
There were no significant differences in the serum area under the concentration-time curve (0-24 h) for free SN-38, at 1,500 and 1,310 μg∙min/mL in the IA and IV groups, respectively (P = .152). The IA group showed significantly higher free SN-38 concentrations in tumor tissues at all time points compared with the IV group (P = .002 at 3 min, P = .011 at 2 h, and P = .047 at 24 h). Histologic findings showed that significantly higher tumor necrosis ratios were observed in the IA group compared with the IV group at 24 hours (P = .028).
Micellar nanoparticles could be a promising IA drug delivery system to achieve high tumor tissue concentrations of SN-38.
