Efficacy of liposomes containing a lipophilic muramyl dipeptide derivative for activating the tumoricidal properties of alveolar macrophages in vivo

We examined the activation to the tumoricidal state of normal F344 rat and C57BL/6 mouse alveolar macrophages (AM) by liposomes containing entrapped hydrophilic muramyl dipeptide (H-MDP) or a lipophilic muramyl dipeptide derivative (MTP-PE) inserted directly into the liposome membranes. The superiority of liposomes containing the lipophilic MTP-PE over liposomes containing H-MDP for in vitro and/or in vivo activation of AM was demonstrated in several experiments. First, the i.v. injection of liposomes containing a dose of MTP-PE equal to H-MDP led to higher levels of AM-mediated cytotoxicity as measured by in vitro assay. Second, AM harvested from mice given i.v. injections of liposomes containing MTP-PE maintained their tumoricidal activity for a longer period (5 days) than AM harvested from mice given i.v. injections of liposomes containing H-MDP (3 days). Similar results were obtained from experiments of AM activation in vitro. These data demonstrate that, for the in situ activation of AM, liposomes containing a lipophilic derivative of muramyl dipeptide are superior to liposomes containing hydrophilic muramyl dipeptide.