Disposition of Liposomal Cepharanthine after Intraperitoneal Administration in Mice

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We have recently reported that cepharanthine (CEP) incorporated in liposomes increased IgM antibody production to a greater extent than CEP solution [Shinoda, et al.; Drug Delivery System, 10: 43-48 (1995)]. In order to provide some insights into the relationship between the immuno-modulating activity of liposomal CEP and its biodistribution, this study examined the disposition of liposomal CEP after intraperitoneal (i.p.) administration to mice in comparison with CEP solution. The liposomes were composed of egg phosphatidylcholine and cholesterol in a molar ratio of 7 : 2. Multilamellar liposomes (MLV) were prepared by vortexing dried lipid films, and small unilamellar liposomes (SUV) by ultrasonication of MLV. CEP-containing liposomes and CEP solution (as a control) were injected intraperitoneally to mice. The half-life and mean residence time of CEP were longer after administration of liposomal CEP compared with CEP solution. After CEP injection in liposomes or solution, the mean transit time of CEP in the spleen was higher than those in the liver and lung. However, the liposomes containing CEP reduced the tissue distribution of CEP into the liver, lung, and spleen, compared with CEP solution. In conclusion, it was suggested that immuno-modulating action of CEP may not be directly related to the in vivo disposition of CEP.