Stealth liposomal 5-fluorouracil with or without degradable starch microspheres for hepatic arterial infusion in the treatment of liver metastases. An animal study in VX-2 liver tumor-bearing rabbits.

PURPOSE: Regional application of cytostatics in liver metastases leads to increased concentrations in tumor tissue. Flow retardation by temporary occlusion and drug targeting via liposome encapsulation (PEG liposomes) will further increase tumor concentrations.
MATERIALS AND METHODS: Liver tumor-bearing rabbits were submitted to i.v. or i.a. therapy with or without liposome-encapsulated 5-fluorouracil (5-FU). I.a. groups were additionally treated with or without degradable starch microspheres. Tumor concentrations were calculated by HPLC as area under the curve (AUC).
RESULTS: A comparison with i.v.-applied 5-FU yielded the following increasing concentrations: 5-FU-PEG liposomes i.v. 6-fold, 5-FU i.a. 20-fold, 5-FU i.a. + DSM 226-fold, 5-FU-PEG liposomes i.a. 319-fold, 5-FU-PEG liposomes i.a. + DSM 2203-fold.
CONCLUSION: The intratumoral concentration of 5-FU was increased up to 2203 times the intravenous dose by combination of regional application via the hepatic artery with temporary embolization by degradable starch microspheres and drug targeting by liposome encapsulated 5-FU.