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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.
AuthorsC Laduron, A Coune, G Atassi, J Hildebrand, J M Ruysschaert, P Stryckmans, C Brassinne
JournalResearch 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
PMID6190203 (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

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