TY - JOUR
T1 - Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model
AU - Gabizon, A.
AU - Goren, D.
AU - Fuks, Z.
AU - Meshorer, A.
AU - Barenholz, Y.
PY - 1985/5
Y1 - 1985/5
N2 - We have examined the anti-tumour activity of liposome-entrapped Adriamycin in a murine metastatic tumour model produced by i.v. inoculation of J-6456 lymphoma cells and affecting predominantly the liver. Sonicated liposomes containing phosphatidylcholine, a negatively-charged phospholipid and cholesterol were used in these experiments. Liposome-entrapped Adriamycin was more effective than free Adriamycin at equivalent doses of the drug. The superior thereapeutic effect of the liposome-associated drug was manifest, either with a single i.v. treatment using a dose bordering the toxicity threshold of free Adriamycin or with a multi-injection schedule using smaller doses. Based on the growth kinetics data of the J- 6456 lymphoma, our results indicate that tumour cell killing was enhanced by a factor of ˜ 100 using the liposome associated form of Adriamycin. Histopathologic studies in mice bearing well-established metastases of the J-6456 lymphoma in liver and spleen indicated that the extent and duration of pathologic remission were significantly improved in mice receiving the liposome-entrapped drug as compared to mice receiving free drug. No significant differences in the anti-tumour effect of liposome entrapped Adriamycin were observed replacing phosphatidylserine by phosphatidylglycerol and reducing the cholesterol:phospholipid molar ratio from 100% to 25%. In contrast to the metastatic tumour model, liposome-entrapped Adriamycin was significantly less effective than free Adriamycin on the local i.m. growth of the J-6456 tumour. Altogether the survival and histopathological data presented suggest that, with regard to a group of neoplastic conditions with a predominant pattern of liver dissemination, a substantial increase in the therapeutic index of Adriamycin can be achieved in a selective manner with the use of liposomes.
AB - We have examined the anti-tumour activity of liposome-entrapped Adriamycin in a murine metastatic tumour model produced by i.v. inoculation of J-6456 lymphoma cells and affecting predominantly the liver. Sonicated liposomes containing phosphatidylcholine, a negatively-charged phospholipid and cholesterol were used in these experiments. Liposome-entrapped Adriamycin was more effective than free Adriamycin at equivalent doses of the drug. The superior thereapeutic effect of the liposome-associated drug was manifest, either with a single i.v. treatment using a dose bordering the toxicity threshold of free Adriamycin or with a multi-injection schedule using smaller doses. Based on the growth kinetics data of the J- 6456 lymphoma, our results indicate that tumour cell killing was enhanced by a factor of ˜ 100 using the liposome associated form of Adriamycin. Histopathologic studies in mice bearing well-established metastases of the J-6456 lymphoma in liver and spleen indicated that the extent and duration of pathologic remission were significantly improved in mice receiving the liposome-entrapped drug as compared to mice receiving free drug. No significant differences in the anti-tumour effect of liposome entrapped Adriamycin were observed replacing phosphatidylserine by phosphatidylglycerol and reducing the cholesterol:phospholipid molar ratio from 100% to 25%. In contrast to the metastatic tumour model, liposome-entrapped Adriamycin was significantly less effective than free Adriamycin on the local i.m. growth of the J-6456 tumour. Altogether the survival and histopathological data presented suggest that, with regard to a group of neoplastic conditions with a predominant pattern of liver dissemination, a substantial increase in the therapeutic index of Adriamycin can be achieved in a selective manner with the use of liposomes.
UR - http://www.scopus.com/inward/record.url?scp=0021920756&partnerID=8YFLogxK
U2 - 10.1038/bjc.1985.103
DO - 10.1038/bjc.1985.103
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C2 - 3994911
AN - SCOPUS:0021920756
SN - 0007-0920
VL - 51
SP - 681
EP - 689
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 5
ER -