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-glucuron ide (PGlcUA) have a long-circulation time and tend to accumulate in th e tumors of tumor-bearing mice. Taking advantage of this character, we investigated the therapeutic effect of vincristine (VCR) encapsulated in liposomes containing PGlcUA (dipalmitoylphosphatidylcholine/choles terol/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 lip osomal VCR was injected intravenously into BALB/c mice bearing Meth A sarcoma implanted subcutaneously 5 days before hand. Single-dose admin istration of VCR (3.0 mg/kg) in PGlcUA-liposomes significantly suppres sed tumor growth, and prolonged the survival time (T/C = 1.37). Furthe rmore, 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 i nstead of PGlcUA. PGlcUA-liposomes might thus be a useful tool for del ivering antitumor agents to tumor tissues.