Abstract
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 therapeutic 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 approximately 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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 24 print issues and online access
$259.00 per year
only $10.79 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Rights and permissions
About this article
Cite this article
Gabizon, A., Goren, D., Fuks, Z. et al. Superior therapeutic activity of liposome-associated adriamycin in a murine metastatic tumour model. Br J Cancer 51, 681–689 (1985). https://doi.org/10.1038/bjc.1985.103
Issue Date:
DOI: https://doi.org/10.1038/bjc.1985.103
This article is cited by
-
Antitumor effects of adriamycin encapsulated in liposomes on chemically induced malignant fibrous histiocytoma in rats: Histological aspects*
Journal of Orthopaedic Science (1997)
-
A phase II trial of Doxorubicin HCl Liposome Injection in patients with advanced pancreatic adenocarcinoma
Investigational New Drugs (1995)
-
A two-step targeting approach for delivery of doxorubicin-loaded liposomes to tumour cells in vivo
Cancer Chemotherapy and Pharmacology (1995)
-
Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)
Investigational New Drugs (1994)
-
Organ distribution and antitumor activity of free and liposomal doxorubicin injected into the hepatic artery
Cancer Chemotherapy and Pharmacology (1993)