Inhibitory effect of liposomal MDP-Lys on lung metastasis of transplantable osteosarcoma in hamster.
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 microg/day) and liposomal MDP-Lys (20 microg 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 microg twice/week was effective for inhibiting lung metastasis at a far lower dose of MDP-Lys than that given as a solution (40 microg vs. 350 microg 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.
Nitta
Y
Y
Department of Orthopaedic Surgery, Hiroshima University School of Medicine, Japan.
Sugita
T
T
Ikuta
Y
Y
Murakami
T
T
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D000818:Animals; D001835:Body Weight; D001859:Bone Neoplasms / Q000473:pathology*; D006224:Cricetinae; D008081:Liposomes; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D008297:Male; D008648:Mesoderm / Q000473:pathology; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000517:prevention & control* / Q000556:secondary; D016019:Survival Analysis; D013997:Time Factors
D008081:Liposomes; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C036866:romurtide