Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor

Abstract

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.

Pharmacokinetics and Tissue Distribution of Etoposide Delivered in Parenteral Emulsion

“…The major limiting step in the formulation of etoposide is its lipophilicity, and vehicles used as solubilizers are associated with adverse side effects such as hypotension, anaphylaxis, bronchospasm, etc 3,4. Etoposide commercial formulations upon intravenous administration eliminated rapidly from the blood circulation and produced myelosuppression 5. However, the effects of etoposide depend not only on its concentration but also on the duration of action 6.…”

Folate-targeted etoposide-encapsulated lipid nanospheres

“…Etoposide when encapsulated in liposomes produced lower side effects, improved pharmacokinetics, and anticancer activity than the commercial etoposide formulation (Sengupta et al 2000(Sengupta et al , 2001. In our previous study, we have shown that etoposideencapsulated lipid nanospheres are stable and produced improved anticancer activity compared with commercial etoposide formulation.…”

Tuftsin Augments Antitumor Efficacy of Liposomized Etoposide against Fibrosarcoma in Swiss Albino Mice

“…One possible solution is the use of drug delivery systems that can specifically deliver anticancer drugs solely to tumor tissues. ETP entrapped in liposomes has been found to be an effective application of this method (19,24). Liposomes are lipidbased vesicles that enable efficient and targeted delivery of drugs to the desired site (15,17).…”

“…Earlier attempts have demonstrated usage of liposomized ETP (Lip-ETP) in delaying tumor progression, but such treatment failed to regress tumor in model animals (19,24). In the present study, we evaluated tuftsin-mediated augmentation of the antitumorogenic potential of ETP against fibrosarcoma induced in Swiss albino mice by the carcinogen benzo (a) pyrene.…”