Inhibitory Effect of Liposomal MDP-Lys on Lung Metastasis of Transplantable Osteosarcoma in Hamster

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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.

Keywords: Key words: Osteosarcoma; Lung metastasis; MDP-Lys;

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/000000001108747417

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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  • Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
    Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.
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