title: Intraarterial Therapy Using Micellar Nanoparticles Incorporating SN-38 in a Rabbit Liver Tumor Model.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Micellar nanoparticles could be a promising IA drug delivery system to achieve high tumor tissue concentrations of SN-38.
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara. Electronic address: hmn@naramed-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nishiofuku
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Fukuoka
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Masada
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Shota
authors.initials: S
authors.lastname: Tatsumoto
authors.affiliation: Departments of Surgery, Nara Medical University, Kashihara.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sho
authors.affiliation: Departments of Surgery, Nara Medical University, Kashihara.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yamato
authors.affiliation: Departments of Surgery, Nara Medical University, Kashihara.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yasuda
authors.affiliation: Department of Diagnostic and Interventional Radiology, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Matsushima
authors.affiliation: Diagnostic Pathology, Nara Medical University, Kashihara.
authors.forename: Masato
authors.initials: M
authors.lastname: Takano
authors.affiliation: Diagnostic Pathology, Nara Medical University, Kashihara.
authors.forename: Chiho
authors.initials: C
authors.lastname: Ohbayashi
authors.affiliation: Department of Radiology and Interventional Radiology Center, Nara Medical University, Kashihara.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kichikawa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D019540:Area Under Curve; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D005260:Female; D005268:Femoral Vein; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008823:Micelles; D053758:Nanoparticles; D009336:Necrosis; D011817:Rabbits; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D000077146:Irinotecan; D002166:Camptothecin