The effect of adriamycin against a liver metastatic model by encapsulation in liposomes.
Antitumor activities of liposomes containing adriamycin (L-ADM) and their distribution process into tumour cells were analysed. The lipid composition of the liposomes was dimyristoylphosphatidylglycerol (DMPG)/egg phosphatidylcholine/cholesterol/adriamycin (ADM) in a molar ratio of 11.4:2:12:1.3. Liver-metastasizing murine tumour models, M5076 and L5178Y-ML, were used. In vivo antitumour effect against these tumour models was assessed from increase in life span (ILS). The survival prolongation effect of L-ADM in mice with liver failure caused by M5076 was significantly higher than that of F-ADM. In contrast, significant enhancement of the effects by encapsulation in liposomes was not observed in L5178Y-ML-bearing mice. In vitro cytostatic activities of L-ADM against M5076 cells as well as against other tumour cell lines were lower than those of F-ADM. The in vitro kinetic study on the distribution of L-ADM to the tumour cells revealed that ADM in L-ADM was taken up into the tumour cells mainly after it was released from the liposomes rather than taken up as the liposomal form. Among the cell lines tested, M5076 cells had the highest phagocytic activity and therefore the highest uptake activity of ADM during incubation with L-ADM. These findings suggest that the augmented antitumour activity of L-ADM in M5076-bearing mice was the result of phagocytosis of L-ADM by M5076 cells as well as the reduction of toxicity, prolonged retention of ADM in systemic circulation, and liver accumulation of ADM after administration of L-ADM.
Yachi
K
K
Basic Technology Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Suzuki
N
N
Tanaka
N
N
Okada
K
K
Mitsui
I
I
Kawato
Y
Y
Komagata
Y
Y
Komiyama
K
K
Kikuchi
H
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003470:Culture Media; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D054747:Histiocytic Sarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D003470:Culture Media; D008081:Liposomes; D004317:Doxorubicin