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Research Paper Open Access
The monensin, known to enhance the cytotoxicity of ricin and ricin-based immunotoxins is a very hydrophobic molecule and this limits its administration in optimum doses under in vivo conditions. In order to realise its full potential, monensin was intercalated into various liposomal formulations and its ability to potentiate the cytotoxicity of ricin liposomes in human epidermoid carcinoma (KB) cells was studied. It was observed that ricin cytotoxicity enhancing ability of monensin liposome depends on the surface charge as well as density and chain length of distearoyl phosphatidylethanolamine-methoxy polyethylene glycol present on the surface of liposomal monensin. Maximum potentiation on the cytotoxicity of liposomal ricin was observed by monensin entrapped in neutral liposome (106.5 fold) followed by negatively charged (94.2 fold) and positively charged liposome (90 fold). Studies on the effect of variation of density and chain length of distearoyl phosphatidylethanolamine-methoxy polyethylene glycol showed that neutral monensin liposomes having 2.5 mol% distearoyl phosphatidylethanolamine-methoxy polyethylene glycol with chain length of 2000 exhibits maximum potentiation (117.6 fold) on the cytotoxicity of ricin liposomes when the cellular uptake of monensin liposome was maximum (42.0%) and the zeta potential value on the surface of liposomes was −0.645. The present study has clearly shown that liposomal monensin is very effective in enhancing the cytotoxicity of liposomal ricin in human cancer cells and liposome can be used as in vivo deliver vehicle for monensin to potentiate the cytotoxicity of liposomal ricin to eliminate cancer cells.
Human cancer cells, liposomal monensin, liposomal ricin, sterically stabilized liposomes, zeta potential