The ability of
liposomes containing a synthetic lipophilic
muramyl dipeptide derivative, N-acetylmuramyl-L-alanyl-D-isoglutamyl-sn-
glycerol dipalmitate (
MDP-GDP), to inhibit the growth of experimental B16-F1
melanoma liver
metastases in syngeneic C57BL/6 mice has been determined. Multiple i.v.
injections of
distearoylphosphatidylcholine:
dimyristoylphosphatidylglycerol liposomes (1 mumol, 10:1 molar ratio) containing 0.1 to 1 microgram of
MDP-GDP given at 3- to 4-day intervals after seeding the livers with
tumor cells resulted in a significant inhibition of the number of experimental B16 liver
metastases. Control
liposomes or free MDP (100 micrograms) failed to affect the number of experimental
metastases. A single prophylactic injection of
liposomes containing
MDP-GDP was equally effective in eliciting a reduction in the number of experimental liver
metastases. The ability of liposomal
MDP-GDP to inhibit the growth of liver
metastases correlated with its ability to induce Kupffer cell tumoricidal activity against the
tumor cell targets; activation of C57BL/6 Kupffer cell activity in vitro was most effective with liposomal
MDP-GDP, followed by liposomal MDP and free MDP. Only liposomal
MDP-GDP and liposomal MDP were able to induce Kupffer cell tumoricidal activity in situ, free MDP being inactive. Liposomal
muramyl dipeptide therapy using lipophilic derivatives would appear to be an effective treatment for hepatic
metastases derived from primary
tumors.