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.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Department of Surgery, Charité, Universitaetsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
U
U
Pohlen
R
R
Reszka
P
P
Schneider
H J
HJ
Buhr
G
G
Berger
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D002851:Chromatography, High Pressure Liquid; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D008863:Microspheres; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics; D011817:Rabbits; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D008081:Liposomes; D011092:Polyethylene Glycols; D005472:Fluorouracil