Effects of administered route on tissue distribution and antitumor activity of polyethyleneglycol-coated liposomes containing adriamycin.
Tissue distribution, antitumor activity and side effects after intraperitoneal administration of polyethyleneglycol-coated liposomes containing adriamycin (PEG-LADR) were examined and compared to that after intravenous treatment. Plain liposomes (PLADR) and PEG-LADR appeared to maintain blood circulation by intraperitoneal injection and suggested usefulness in passive targeting. Because of the accumulation of ADR in the pancreas found after intraperitoneal treatment, this administered route of PLADR and PEG-LADR was expected to be useful as a method of targeting the pancreas. The side effects of ADR in the heart and liver were suppressed by the liposomalization and PEG-modification. The antitumor effect of ADR was increased by the liposomalization, and PEG-modification after intraperitoneal administration was superior to that after intravenous administration. The slowly disappearing pattern of PLADR and PEG-LADR from the abdominal cavity was similar. It is suggested that PLADR and PEG-LADR were absorbed intact from the abdominal cavity and transferred into the blood circulation.
Sadzuka
Y
Y
University of Shizuoka, Shizuoka-shi, Shizuoka-ken, Japan.
Nakai
S
S
Miyagishima
A
A
Nozawa
Y
Y
Hirota
S
S
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology*; D004334:Drug Administration Schedule; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008054:Lipid Peroxides / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011092:Polyethylene Glycols / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000903:Antibiotics, Antineoplastic; D008054:Lipid Peroxides; D008081:Liposomes; D011092:Polyethylene Glycols; D004317:Doxorubicin