Intraperitoneal (IP)
therapy with
platinum (Pt)-based drugs has shown promising results clinically; however, high locoregional concentration of the
drug could lead to adverse side effects. In this study, IP administration was coupled with a
folate receptor-targeted (FRT) liposomal system, in an attempt to achieve intracellular delivery of the Pt-based
drug carboplatin in order to increase therapeutic efficacy and to minimize toxicity. In vitro and in vivo activity of FRT
carboplatin liposomes was compared with the activity of free
drug and nontargeted (NT)
carboplatin liposomes using FR-overexpressing IGROV-1
ovarian cancer cells as the model. Significant reduction in cell viability was observed with FRT
liposomes, which, compared with the free
drug, provided an approximately twofold increase in
carboplatin potency. The increase in
drug potency was correlated with significantly higher cellular accumulation of Pt resulting from FRT liposomal delivery. Further evaluation was conducted in mice bearing intraperitoneally inoculated IGROV-1 ovarian
tumor xenografts. A superior survival rate (five out of six animals) was achieved in animals treated with FRT
carboplatin liposomes, injected intraperitoneally with a dose of 15 mg/kg and following a schedule of twice-weekly administration for 3 weeks. In contrast, no survivors were observed in the free
drug or NT
carboplatin liposome groups. The presence of
cancer cells in lung and liver tissues was observed in the saline, free
carboplatin, and NT
carboplatin liposome groups. However, there was no sign of
cancer cells or
drug-related toxicity detected in tissues from the animals treated with FRT
carboplatin liposomes. The results of this study have demonstrated for the first time that the approach of coupling IP administration with FRT liposomal delivery could provide significantly improved therapeutic efficacy of
carboplatin in the treatment of metastatic
ovarian cancer.