Micellar electrokinetic capillary chromatography reveals differences in intracellular metabolism between liposomal and free doxorubicin treatment of human leukemia cells.
Doxil is a pegylated liposome formulation of the anthracycline doxorubicin. To better explain observed differences in the toxicity of Doxil and free doxorubicin in solution, the intracellular metabolism of the formulations after treatment in CCRF-CEM and CEM/C2 human leukemia cell lines was investigated. Using micellar electrokinetic capillary chromatography with laser-induced fluorescence detection, with a 63 zepto (10(-21)) mole doxorubicin limit of detection, five common metabolites and doxorubicin were detected upon treatment with both of these drug delivery systems. Two unique metabolites appeared with the Doxil and two unique metabolites appeared with the free doxorubicin delivery systems. For common metabolites, the relative amount of metabolite generated from Doxil was approximately 10 times higher than for free doxorubicin.
Eder
Angela R
AR
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Arriaga
Edgar A
EA
D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D004304:Dosage Forms; D004317:Doxorubicin / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D000970:Antineoplastic Agents; D004304:Dosage Forms; D008081:Liposomes; D004317:Doxorubicin