Encapsulation in cationic liposomes enhances antitumour efficacy and reduces the toxicity of etoposide, a topo-isomerase II inhibitor

Etoposide exerts its antineoplastic effect by forming a ternary complex wit h 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 efficac y and reduce the toxicity of antineoplastic agents. Recent evidence suggest s that cationic liposomes bind efficiently to tumours. The present study wa s thus designed to encapsulate etoposide in cationic liposomes and to evalu ate its antitumour efficacy and systemic toxicity in comparison with a conv entional parenteral formulation. Etoposide encapsulated in liposomes was sy nthesised by thin film hydration followed by an extrusion method. Fibrosarc oma was induced in mice by subcutaneous administration of 20-methylcholanth rene. Chemotherapy was started when the tumour reached 200 mm(3) in volume. Liposomal etoposide (10 mg/m(2)/day for 5 days) significantly delayed tumo ur 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, n on-liposomal-etoposide- and liposomal-etoposide-treated groups, respectivel y, A transient reduction in body weight was seen in both the liposomal- and nonliposomal-etoposide-treated groups. The maximum tolerated dose was howe ver significantly higher in the group treated with liposomal etoposide, whi ch also exhibited a lesser degree of myelosuppression than the animals trea ted with non-liposomal etoposide. The present findings suggest that cationi c liposomes could be considered as potential for delivery of etoposide to t umours. Copyright (C) 2001 S. Karger AG, Basel.