Liposomes have been used in recent years as carriers for drugs and molecules of
biological importance. In
cancer chemotherapy, however, the advantages of
liposome encapsulation of
antitumor drugs remain uncertain, with the possible exception of the usefulness of encapsulated 1-beta-D-arabinofuranosyl-cytosine (
ara-C), an
antitumor drug of a very short half-life.
Liposome-encapsulated
ara-C has been shown by others to enhance significantly the survival time of mice bearing
leukemia, and the enhancement may be attributable to the role of
liposomes as a slow release system for
ara-C. We now further explore the advantages of two sustained release systems for
ara-C, namely the
liposome-encapsulated
ara-C and 1-beta-D-arabinofuranosylcytosine-5'-diphosphate-L-1,2-dipalmitin (ara-
CDP-L-
dipalmitin, a
prodrug of
ara-C). Intravenously implanted
Lewis lung carcinoma is used as a solid
tumor model. The therapeutic effectiveness of the two slow release forms of
ara-C given by either i.v. or i.p.
injections is examined. Viable
tumor cells (1.0 X 10(5) cells/mouse) were inoculated i.v. and treatment was initiated 24 hr later using three schedules of multiple treatments for liposomal
ara-C and single or multiple
injections of ara-
CDP-L-
dipalmitin. Liposomal
ara-C given by the i.p. route consistently increased the number of cures (greater than 120 days survival). For example, when nine small doses (10 mg/kg) were given on consecutive days by i.p.
injections, 50% of mice given liposomal
ara-C were cured, compared with 10% cures in the group given
ara-C liposomes by i.v. and no cures in mice receiving free
ara-C given according to the same schedules. On the other hand, ara-
CDP-L-
dipalmitin given at a single dose is more effective than an equal dose divided in five
injections. However, no cures have been obtained by treatments with ara-
CDP-L-
dipalmitin. These results have further demonstrated the advantage of
liposomes as carriers for
antitumor drugs of short half-life.