Improvement of biodistribution with PEGylated liposomes containing docetaxel with degradable starch microspheres for hepatic arterial infusion in the treatment of liver metastases: a study in CC-531 liver tumor-bearing WAG RIJ rats

Anticancer Res. 2011 Jan;31(1):153-9.

Abstract

Aim: To improve the drug concentration in liver metastases, docetaxel was encapsulated in polyethyleneglycol-liposomes and administered regionally with degradable starch microspheres (DSM).

Materials and methods: A rodent model of solitary metastasis (CC-531 adenocarcinoma) was studied. The animals were randomized into six groups and treated with 15 ng/kg docetaxel: I: intravenous (i.v.). II: PEG-liposomes i.v.; III: intraartial (i.a.) via the hepatica artery; IV: i.a.) + DSM; V: PEG-liposomes i.a.; and VI: PEG-liposomes i.a. + DSM. The docetaxel concentration in the serum, liver and liver tumor at defined times (5, 15, 30, 60,120 240 min and 24 h) was measured using HPLC.

Results: The area under the concentration (AUC) versus time curves showed an 11-fold higher concentration in the tumor tissue when comparing the docetaxel-PEG-liposomes i.a. + DSM group to the i.v. group (p<0.01).

Conclusion: Compared to intravenous therapy, i.a. therapy with docetaxel-PEG-liposomes + DSM results in higher tumor tissue concentrations.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cell Proliferation
  • Docetaxel
  • Embolization, Therapeutic
  • Hepatic Artery*
  • Infusions, Intra-Arterial
  • Liposomes
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / secondary
  • Magnetic Resonance Imaging
  • Polyethylene Glycols*
  • Rats
  • Starch / administration & dosage*
  • Taxoids / therapeutic use*

Substances

  • Antineoplastic Agents
  • Liposomes
  • Taxoids
  • degradable starch microspheres
  • Docetaxel
  • Polyethylene Glycols
  • Starch