Tyagi N, Rathore S S, Ghosh P C
Department of Oncologic Sciences, Mitchel Cancer Institute, University of South Alabama, Mobile, Alabama, USA.
Indian J Pharm Sci. 2013 Jan;75(1):16-22. doi: 10.4103/0250-474X.113533.
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.
莫能菌素已知可增强蓖麻毒素和基于蓖麻毒素的免疫毒素的细胞毒性，它是一种非常疏水的分子，这限制了其在体内条件下以最佳剂量给药。为了充分发挥其潜力，将莫能菌素插入各种脂质体制剂中，并研究了其增强蓖麻毒素脂质体对人表皮样癌（KB）细胞细胞毒性的能力。观察到莫能菌素脂质体增强蓖麻毒素细胞毒性的能力取决于脂质体莫能菌素表面存在的二硬脂酰磷脂酰乙醇胺 - 甲氧基聚乙二醇的表面电荷、密度和链长。包裹在中性脂质体中的莫能菌素对脂质体蓖麻毒素细胞毒性的增强作用最大（106.5倍），其次是带负电荷的脂质体（94.2倍）和带正电荷的脂质体（90倍）。对二硬脂酰磷脂酰乙醇胺 - 甲氧基聚乙二醇密度和链长变化的影响研究表明，当莫能菌素脂质体的细胞摄取量最大（42.0%）且脂质体表面的ζ电位值为 -0.645时，含有2.5 mol%链长为2000的二硬脂酰磷脂酰乙醇胺 - 甲氧基聚乙二醇的中性莫能菌素脂质体对蓖麻毒素脂质体的细胞毒性表现出最大的增强作用（117.6倍）。本研究清楚地表明，脂质体莫能菌素在增强脂质体蓖麻毒素对人癌细胞的细胞毒性方面非常有效，并且脂质体可作为莫能菌素的体内递送载体，以增强脂质体蓖麻毒素的细胞毒性来消除癌细胞。
