Treatment of l1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-β-D-arabinofuranosyl cytosine

✍ Scribed by R. A. Schwendener; H. Schott

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: French
• Weight: 490 KB
• Volume: 51
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910510321

✦ Synopsis

N4-alkyl-I -P-D-arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti-tumor drug I -P-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 antitumor effect against the murine LIZ10 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 LI 2 I0 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.