Premium
Treatment of l1210 murine leukemia with liposome‐incorporated N 4 ‐hexadecyl‐1‐β‐D‐arabinofuranosyl cytosine
Author(s) -
Schwendener R. A.,
Schott H.
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910510321
Subject(s) - liposome , prodrug , l1210 cells , alkyl , chemistry , leukemia , cytosine , cytarabine , lymphoid leukemia , cytotoxicity , pharmacology , combinatorial chemistry , biochemistry , biology , in vitro , organic chemistry , immunology , dna
N 4 ‐alkyl‐1‐β‐D‐arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti‐tumor drug 1 ‐β‐D‐arabinofurano sylcytosine (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 L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara‐C. The N 4 ‐alkyl‐ara‐C derivatives with alkyl chains containing 14–16 C‐atoms were highly effective against L1 210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N 4 ‐alkyl‐ara‐C derivatives and the improved anti‐tumor effect of the liposomal N 4 ‐hexadecyl‐ara‐C preparation compared to other known N 4 ‐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.