Inhibitory effect of liposomal MDP-Lys on lung metastasis of transplantable osteosarcoma in hamster

MDP-Lys (N-2-[(N-acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N-6-stearoyl-L-ly sine) a macrophage activator, is a lipophilic derivative of muramyl dipepti de (MDP). Multilamellar liposome incorporated MDP-Lys was prepared using ph osphatidylcholine and phosphatidylserine by conventional film method, and i ts inhibitory effect on lung metastasis was compared with MDP-Lys as a solu tion in hamster's osteosarcoma. The lung metastatic rates after transplanta tion of the tumor to a lower extremity, in which the extremity was amputate d 3 weeks later, were 50% and 100% 3 and 7 weeks, respectively, after trans plantation. The rates after amputation were reduced by the treatment with M DP-Lys proportionally to the logarithmic MDP Lys dose, and the rates 7 week s after transplantation were 55% and 60%, respectively, in the MDP-Lys solu tion (50 mu g/day) and liposomal MDP-Lys (20 mu g twice/week) groups. Fifty percent of hamsters treated with liposomal MDP-Lys survived for more than 6 months. Considering that hamsters had a lung metastasis rate of 50% befor e MDP-Lys treatment, liposomal MDP-Lys given at a dose of 20 mu g twice /we ek was effective for inhibiting lung metastasis at a far lower dose of MDP- Lys than that given as a solution (40 mu g vs. 350 mu g per week). No signi ficant side effect of liposomal MDP-Lys, as evaluated by the comparison of body weight changes among differently treated hamsters, was detected. This greater inhibitory effect of liposomal MDP-Lys can be considered to be due to the longer retention of the liposomal form in the lung.