In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors

J Vasc Interv Radiol. 2012 Mar;23(3):397-404.e1. doi: 10.1016/j.jvir.2011.10.024. Epub 2011 Dec 29.

Abstract

Purpose: To investigate the pharmacokinetics and efficacy of chemoembolization with a cisplatin-loaded superabsorbent polymer (SAP) suspension in a rabbit model with transplanted liver VX2 tumors.

Materials and methods: VX2 tumors were implanted into the left lobe of the liver in eight rabbits. Embolization of the proper hepatic artery was performed with cisplatin-loaded or unloaded SAP. In the cisplatin-loaded SAP group (n = 4), 5 mg of SAP (106-150 μm) loading 2.35 mg of cisplatin and 0.5 mL of ionic contrast material (ioxaglic acid 320 mgI/mL) was injected into the proper hepatic artery. In the control group (hepatic arterial infusion [HAI] + SAP; n = 4), 5 mg of SAP loading 0.5 mL of ioxaglic acid alone was injected after a bolus infusion of an equivalent amount of cisplatin. Sequential change of the plasma platinum concentration within the first 24 hours was measured. Blood sampling and histopathologic examination were performed at 1-week follow-up. Magnetic resonance (MR) images were used to calculate the growth rate of the VX2 tumor.

Results: All animals underwent successful embolization. Both total and free plasma platinum mean concentrations within the first 24 hours remained lower in the cisplatin-loaded SAP group, although without statistical significance (P > .05). The mean tumor growth rate was significantly lower in the cisplatin-loaded SAP group than the control group (20% vs 116%; P = .049). Histopathologic examination revealed coagulative necrosis to nontumorous liver parenchyma in two rabbits in the cisplatin-loaded SAP group, although no deaths occurred.

Conclusions: These results suggested that chemoembolization with cisplatin-loaded SAP was a safe and tolerable treatment and was more effective in suppressing the tumor growth.

MeSH terms

  • Acrylic Resins / chemistry*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / blood
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / toxicity
  • Chemoembolization, Therapeutic* / adverse effects
  • Cisplatin / administration & dosage*
  • Cisplatin / blood
  • Cisplatin / pharmacokinetics
  • Cisplatin / toxicity
  • Contrast Media / administration & dosage
  • Drug Carriers*
  • Hepatic Artery
  • Infusions, Intra-Arterial
  • Ioxaglic Acid / administration & dosage
  • Liver Neoplasms, Experimental / blood supply
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / pathology
  • Magnetic Resonance Imaging
  • Microspheres
  • Polyvinyls / chemistry*
  • Rabbits
  • Tumor Burden / drug effects

Substances

  • Acrylic Resins
  • Antineoplastic Agents
  • Contrast Media
  • Drug Carriers
  • Polyvinyls
  • acrylic acid-vinyl alcohol copolymer
  • Cisplatin
  • Ioxaglic Acid