Preparation of low density lipoprotein-9-methoxy-ellipticin complex and its cytotoxic effect against L1210 and P 388 leukemic cells in vitro.
Previous studies have suggested that low density lipoprotein (LDL) may be used as a drug targeting carrier for chemotherapeutic agents to neoplastic cells. In this study the cytotoxic agent 9-methoxy-ellipticin (MeOE) was incorporated into dimirystoyl phosphatidylcholine, cholesteryl oleate stabilized microemulsion and the latter fused with human LDL. Both agarose electrophoresis migration and the electron microscopic shape of the drug-LDL complexes were similar to those of native LDL. The in vitro cytotoxic tests on L1210 and P388 leukemic cells demonstrated that the complex was able to kill cells and was more effective than the free drug. This cytotoxic activity of the drug-LDL complex depends on the LDL high affinity receptor: the native LDL reduces the killing power. In contrast, methylated LDL, which does not bind to the LDL receptor, has no effect on it. On the other hand, heparin, which prevents binding on the cell surface receptors, partially reduced the cytotoxic activity of the drug-lipoprotein complex. These results suggest that it is possible to incorporate lipophilic cytotoxic drugs into LDL, using a technique of fusion with the microemulsion which contains the drug. This technique allows us to obtain a drug-LDL complex which is able to kill cells via the LDL receptor pathway.
Samadi-Baboli
M
M
Laboratoire de Biochimie, Faculté des Sciences Pharmaceutiques, Toulouse, France.
Favre
G
G
Blancy
E
E
Soula
G
G
D000470:Alkaloids / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers; D004587:Electrophoresis, Agar Gel; D004611:Ellipticines / Q000008:administration & dosage / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008077:Lipoproteins, LDL; D051379:Mice; D008854:Microscopy, Electron; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D000970:Antineoplastic Agents; D004337:Drug Carriers; D004611:Ellipticines; D008077:Lipoproteins, LDL; C001729:9-methoxyellipticine