This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Straubinger, R. M. Articles by Papahadjopoulos, D. Search for Related Content PubMed PubMed Citation Articles by Straubinger, R. M. Articles by Papahadjopoulos, D.

Liposome-based Therapy of Human Ovarian Cancer: Parameters Determining Potency of Negatively Charged and Antibody-targeted Liposomes¹

Cancer Research Institute [R. M. S., N. G. L., R. J. D., K. H., D. P.] and Department of Pharmacology [R. M. S., D. P.], University of California, San Francisco, San Francisco, California 94143-0450

Liposomes containing cytotoxic agents may be highly efficacious for intracavitary therapy of malignancies such as ovarian carcinoma, which resides principally in the peritoneal cavity. We have examined in vitro the cytotoxicity of a variety of liposome-drug formulations against OVCAR-3, a human ovarian cancer cell line. Two drugs tested, methotrexate--aspartate and 5-fluoroorotate, show increased cytotoxicity on various cultured cell lines following encapsulation in liposomes and can be considered liposome-dependent agents. With the optimal lipid composition used in this study, the maximal increase in potency on OVCAR-3 is 2.6-fold for methotrexate--aspartate and 5.2-fold for 5-fluoroorotate. Studies on liposome-cell association suggest a low capacity of OVCAR-3 to bind and internalize phospholipid vesicles, which limits the in vitro potency of liposomes for these cells. OC-125, a monoclonal antibody recognizing an antigen common to a number of human ovarian cancers (CA-125), has been coupled covalently to the liposome surface. Liposomes bearing OC-125 and containing methotrexate--aspartate show an 8-fold increase in potency against OVCAR-3 cells in a 96-h growth inhibition assay. Briefer exposure of tumor cells to treatment accentuates the advantage of targeted liposomes. The cytostatic effect of 1 h exposure to OC-125 liposomes is 100-fold greater than the equivalent exposure to free drug and equal to the maximal cytostatic effect achieved with free drug for 96 h. Attachment of OC-125 antibody also confers upon liposomes the capacity to recognize OVCAR-3 cells growing as an ascites tumor in nude mice. After i.p. injection, control liposomes bind tumor cells in relatively low numbers, while fluorescent OC-125 liposomes can be observed bound specifically to tumor cell masses for periods of days.

¹ This work was supported by grants from the NIH (CA-35340 and CA-25226), the Northern California Cancer Program, and the Academic Senate of the University of California, San Francisco.

² Present address: Department of Pharmaceutics, School of Pharmacy, Cooke Hall, University of New York, Buffalo, NY 14260. CompuServe: 72727, 1036. MacNet: STRAUBINGER.

Received 1/21/88. Revised 4/18/88. Accepted 5/31/88.

This article has been cited by other articles:

				D. C. Drummond, O. Meyer, K. Hong, D. B. Kirpotin, and D. Papahadjopoulos Optimizing Liposomes for Delivery of Chemotherapeutic Agents to Solid Tumors Pharmacol. Rev., December 1, 1999; 51(4): 691 - 744. [Abstract] [Full Text] [PDF]