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Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm³ in volume. Liposomal etoposide (10 mg/m²/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.

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Conventional delivery of etoposide for anticancer therapy is restricted by its lipophilicity and vehicle-associated adverse effects. Liposomes have been reported to increase the ef®cacy and reduce the toxicity of antineoplastic agents. This study was conducted to evaluate novel cationic and sterically-stabilized long-circulating pegylated liposomal formulations of etoposide against JEG3 cell-induced choriocarcinoma xenografts in Balbac nuanu mice.Small unilamellar liposomes loaded with etoposide were prepared by thin-®lm hydration followed by an extrusion method. The total encapsulation of etoposide was 3Á6 and 2Á74 mol % for cationic and pegylated liposomes, respectively. At a dose of 10 mg m À2 aday for 5 days, both the formulations signi®cantly delayed tumour growth and increased the lifespan of the host compared with conventional delivery of etoposide.Liposomes could thus be considered as potential useful carriers for the delivery of etoposide.