Chemotherapeutic efficacy of Nocodazole encapsulated in liposomes on L1210 murine leukemia.

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 dipalmitoyl-phosphatidylcholine: cholesterol: stearylamine (4:3:1) liposomes that were stable at room temperature for at least 48 hr. No drug leakage nor lipid exchange occurred after a 4 hr incubation at 37 degrees C with RPMI 1640 medium supplemented with 10% fetal calf serum. L1210 cells preincubated (2 x 10(6) cells/ml) at 37 degrees C for 3 hr with various concentrations of micronized Nocodazole or liposome-entrapped Nocodazole were injected i.p. into normal CDF1 mice (10(5) 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/day) half the one required with the free compound (50 mg/kg/day). The present data indicate that enclosing Nocodazole, a water insoluble antimitotic compound, in liposomes results in an enhanced therapeutic activity against L1210 murine leukemia.

• Authors: C Laduron, A Coune, G Atassi, J Hildebrand, J M Ruysschaert, P Stryckmans, C Brassinne
• Journal: Research communications in chemical pathology and pharmacology (Res Commun Chem Pathol Pharmacol) Vol. 39 Issue 3 Pg. 419-36 (Mar 1983) ISSN: 0034-5164 [Print] United States
• PMID: 6190203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzimidazoles
• Capsules
• Liposomes
• Nocodazole

Topics

• Animals
• Antineoplastic Agents (administration & dosage)
• Benzimidazoles (administration & dosage)
• Capsules
• Female
• Leukemia L1210 (drug therapy)
• Liposomes
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Nocodazole
• Staining and Labeling