Antitumor activity of vincristine encapsulated in glucuronide-modified long-circulating liposomes in mice bearing Meth A sarcoma.
Liposomes modified with the uronic acid derivative palmityl-D-glucuronide (PGlcUA) have a long circulation time and tend to accumulate in the tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/cholesterol/PGlcUA = 4:4:1 as a molar ratio) on tumor-bearing mice. VCR was loaded into liposomes by a remote loading method, and then free or liposomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose administration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppressed tumor growth, and prolonged the survival time (T/C = 1.37). Furthermore, two-dose administration of the liposomes cured one third of the animals. The therapeutic effect of PGlcUA-liposomes was greater than that of control liposomes containing dipalmitoylphosphatidylglycerol instead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for delivering antitumor agents to tumor tissues.
Tokudome
Y
Y
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Oku
N
N
Doi
K
K
Namba
Y
Y
Okada
S
S
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D004337:Drug Carriers; D005965:Glucuronates; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000188:drug therapy*; D014018:Tissue Distribution; D014750:Vincristine / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D005965:Glucuronates; D008081:Liposomes; D014750:Vincristine