CHEMOTHERAPEUTIC EFFICACY OF NOCODAZOLE ENCAPSULATED IN LIPOSOMES ON L1210 MURINE LEUKEMIA

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 39  (3) , 419-436
Abstract
The use of sonicated phospholipid vesicles (liposomes) as carriers of methyl [5-(2-thienylcarbonyl)-1H-benzimidazol-2-yl] carbamate (Nocodazole), a water insoluble antimitotic compound active on mouse L1210 leukemia was investigated. Nocodazole was incorporated in dipalmitoylphosphatidylcholine:cholesterol:stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 h. No drug leakage nor lipid exchange occurred after a 4 h incubation at 37.degree. C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 .times. 106 cells/ml) at 37.degree. C for 3 h with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (105 cells/mouse). Longest mean survival times and long-time survivors were observed in the group inoculated with L1210 cells preincubated with liposomes containing Nocodazole. CDF1 mice bearing i.p. or i.v. L1210 leukemia were treated i.p. on days 1, 5 and 9 with micronized or liposome-entrapped Nocodazole. Administration of this latter preparation induced a 50% increase in animal life span at the dosage (25 mg/kg per day) half the one required with the free compound (50 mg/kg per day). Enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes evidently results in an enhanced therapeutic activity agains L1210 murine leukemia.