Antibody-Targeted Liposomes to Deliver Doxorubicin to Ovarian Cancer Cells

Abstract

Ovarian cancer is the leading cause of death in women with a gynecologic malignancy. The main reason for the high mortality is the late occurrence of symptoms, resulting in an advanced diseased state at the time of diagnosis. Since ovarian cancer remains confined to the peritoneal cavity virtually throughout its entire clinical course, this type of cancer is an attractive candidate for intraperitoneal chemotherapy. Local instillation of anticancer agents has been used with some success, although systemic absorption of drug, as well as local drug effects, can produce substantial toxicity. This contribution deals with the use of antibody-targeted liposomes (immunoliposomes) for the delivery of doxorubicin to ovarian cancer cells. After a brief discussion of pharmaceutical aspects of the preparation, characterization and stability of OV-17L3 immunoliposomes (anti-ovarian carcinoma Fab' liposomes), me in vitro and in vivo interaction between these specific immunoliposomes and ovarian carcinoma cells are described. A rapid, highly efficient and long-lasting adherence of i.p. administered specific immunoliposomes to i.p. located target cells was observed in a xenograft model of i.p. growing human ovarian carcinoma. However, our preliminary findings on the antitumor activity of doxorubicin-containing immunoliposomes in this xenograft model do not show a therapeutic advantage of specific immunoliposomes over nonspecific liposomes containing doxorubicin. The last part of the article is devoted to an evaluation of the results and discusses potential research directions in the near future.