DEVELOPMENT OF LIPOSOME FORMULATIONS CO-ENCAPSULATING TOPOISOMERASE INHIBITORS IRINOTECAN AND DOXORUBICIN FOR THE TREATMENT OF OVARIAN CANCER

Abstract

Across the globe and in Singapore, ovarian cancer remains the most deadly of the gynaecological cancers and now surpasses cervical cancer in prevalence. Although patients suffering from ovarian cancer respond well to the first line platinum-based chemotherapy, majority of them relapse within a relatively short period of time. At present, there are limited chemotherapy options to treat platinum-resistant ovarian cancer. Thus, there is a need to develop novel treatment regimen that could be useful for patients suffering from platinum-resistant ovarian cancer. Recent clinical trial data have suggested that the combination of doxorubicin and irinotecan may be synergistic when administered together in the treatment of platinum-resistant ovarian carcinoma. With the well-known ability to reduce adverse side effects of the encapsulated drug and deliver the drugs to the tumor site, it is hypothesized that liposomes co-encapsulating doxorubicin and irinotecan in a synergistic ratio would be an appropriate drug delivery system to treat ovarian cancer effectively. The goal of this thesis was to develop liposomes co-encapsulating irinotecan and doxorubicin in synergistic molar ratio of 1:1 for treatment of ovarian cancer. The co-encapsulated liposomal formulation developed through this thesis research exhibited significant anti-tumor activity at two-thirds of the maximum tolerated dose of doxorubicin and one tenth of that of irinotecan in an IGROV-1 ovarian tumor bearing murine model. The results from these studies warrants further testing of this liposome formulation in clinical settings. The success of this project may provide a better alternative to the current treatments to the refractory type of ovarian cancer, and help improve the quality of life of women who are suffering from ovarian cancer worldwide.