Erythrocyte membrane-bound daunorubicin as a delivery system in anticancer treatment.
Drug encapsulation in erythrocytes has been proposed to extend its biological lifetime. Molecules encapsulated this way are protected against rapid cellular metabolism and body elimination. Unfortunately, drugs such as daunorubicin cannot be efficiently entrapped in erythrocytes since drugs diffuse rapidly from the cells. In order to overcome this problem, we have covalently linked daunorubicin to erythrocyte membranes (ghosts) using two different types of linking arms: glutaraldehyde and cis-aconitic acid. Both ghost-daunorubicin conjugates were tested in vitro on mouse leukemia cells (P388D1) and on human osteosarcoma cells (CRL-1427). Results showed a better cytotoxic activity for ghost-glutaraldehyde-daunorubicin conjugate than for ghost-cis-aconityl-daunorubicin conjugate. Both conjugates were also tested in vivo on CDF1 mice bearing P388D1 cells. T/C% of 161 and 103 respectively were observed with ghost-glutaraldehyde-daunorubicin and ghost-cis-aconityl-daunorubicin conjugate at 6.0 mg/kg. Compared to free drug, the increase in survival time could be explained by a slow release of daunomycin in the circulation from the erythrocyte membranes, leading to a more complete absorption by cancer cells.
Gaudreault
R C
RC
Departement de Pharmacologie, Faculté de Médecine, Université Laval, Ste-Foy Qué, Canada.
Bellemare
B
B
Lacroix
J
J
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003630:Daunorubicin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006801:Humans; D007202:Indicators and Reagents; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012516:Osteosarcoma; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D004337:Drug Carriers; D007202:Indicators and Reagents; D003630:Daunorubicin