[Vectorisation of doxorubicin in nanospheres and reversion of pleiotropic resistance of tumor cells].
A multidrug resistance human cell line (Dox-R-MCF7), originating from mammary adenocarcinoma was compared to the drug sensitive parent line (MCF7) to determine whether or not the use of doxorubicin-loaded biodegradable nanospheres (NS-Dox) could circumvent drug resistance. The Dox-R-MCF7 line was shown to resist free doxorubicin (Dox) as the 50% lethal dose for them was 150 times higher than for the sensitive cell-line. Isohexylcyanoacrylate nanospheres, porous matrices of biodegradable innocuous polymer, diameter 300 nm, were loaded with doxorubicin. Free Dox, NS-Dox and Dox-free polymer (NS) were added to the culture medium for 6 hrs. In terms of 50% lethal dose, NS-Dox were cytotoxic for the resistant cell line to an identical extent as for the sensitive parent line. Dox-free nanospheres alone or mixed with free-Dox were noncytotoxic for the resistant line. Drug targetting could be of main importance to overcome multidrug resistance.
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U.R.A.-C.N.R.S. no 1218, Faculté de Pharmacie, Châtenay-Malabry.
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Puisieux
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D001943:Breast Neoplasms / Q000473:pathology; D002461:Cell Line, Transformed / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004337:Drug Carriers; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D014407:Tumor Cells, Cultured
D004337:Drug Carriers; D004317:Doxorubicin
Vectorisation de la doxorubicine dans des nanosphères et réversion de la résistance pléiotropique des cellules tumorales.