Inhibitory Effect of Liposomal MDP-Lys on Lung Metastasis of Transplantable Osteosarcoma in Hamster
Abstract:MDP-Lys (N2-[(N-acetylmuramyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine), a macrophage activator, is a lipophilic derivative of muramyl dipeptide (MDP). Multilamellar liposome incorporated MDP-Lys was prepared using phosphatidylcholine and phosphatidylserine by conventional film method, and its inhibitory effect on lung metastasis was compared with MDP-Lys as a solution in hamster's osteosarcoma. The lung metastatic rates after transplantation of the tumor to a lower extremity, in which the extremity was amputated 3 weeks later, were 50% and 100% 3 and 7 weeks, respectively, after transplantation. The rates after amputation were reduced by the treatment with MDP-Lys proportionally to the logarithmic MDP-Lys dose, and the rates 7 weeks after transplantation were 55% and 60%, respectively, in the MDP-Lys solution (50 μg/day) and liposomal MDP-Lys (20 μg 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% before MDP-Lys treatment, liposomal MDP-Lys given at a dose of 20 μg twice /week was effective for inhibiting lung metastasis at a far lower dose of MDP-Lys than that given as a solution (40 μg vs. 350 μg per week). No significant 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.
Document Type: Research Article
Affiliations: 1: *Department of Orthopaedic Surgery, Hiroshima University School of Medicine. Hiroshima 734-8551, Japan 2: †Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine. Hiroshima 734-8551, Japan
Publication date: January 1, 2001
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