Treatment of L1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-beta-D-arabinofuranosyl cytosine.
N4-alkyl-1-beta-D-arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti-tumor drug 1-beta-D-arabinofuranosylcytosine (ara-C) were synthesized and incorporated into unilamellar liposomes. The resulting preparations yielded stable unilamellar liposomes with diameters ranging between 40 and 70 nm. The liposomal derivatives exhibited an increased anti-tumor effect against the murine L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara-C. The N4-alkyl-ara-C derivatives with alkyl chains containing 14-16 C-atoms were highly effective against L1210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N4-alkyl-ara-C derivatives and the improved anti-tumor effect of the liposomal N4-hexadecyl-ara-C preparation compared to other known N4-acyl-ara-C prodrugs, together with the possibility of preparing large volumes of stable and sterile liposomes, hold out the prospect of more effective chemotherapy for leukemias.
Schwendener
R A
RA
Department of Internal Medicine, University Hospital, Zürich, Switzerland.
Schott
H
H
D000818:Animals; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D007939:Leukemia L1210 / Q000188:drug therapy*; D008081:Liposomes
D004337:Drug Carriers; D008081:Liposomes; D003561:Cytarabine; C074701:N(4)-hexadecyl-1-arabinofuranosylcytosine