Peritoneal dissemination in
gastric cancer is a common fatal clinical condition with few effective
therapies available. We studied the
therapeutic effect of a
tumor-targeting drug delivery system that uses
cisplatin-encapsulated and Tf-conjugated PEG
liposomes (Tf-PEG
liposomes) in nude mice with peritoneal dissemination of human
gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH
liposomes (bare
liposomes) encapsulating
cisplatin were prepared by reverse-phase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG
liposomes were internalized into
tumor cells by receptor-mediated endocytosis. To examine the biodistribution of each
liposome and
cisplatin level, nude mice were inoculated i.p. with 10(7) MKN45P human gastric
tumor cells. On the fourth day after
tumor inoculation, (3)H-CHE-labeled and
cisplatin-encapsulated Tf-PEG, PEG or bare
liposome were inoculated i.p. The Tf-PEG
liposome-administered group maintained high
liposome and
cisplatin levels in
ascites and showed a prolonged residence time in the peripheral circulation. Uptake of Tf-PEG
liposomes into the liver and spleen was significantly lower than that of bare
liposomes. Uptake of Tf-PEG
liposomes in disseminated
tumor cells of
ascites and the greater omentum was significantly higher than that of PEG or bare
liposomes and a significant increase in
cisplatin levels was observed in these
tumor cells. Mice receiving Tf-PEG
liposomes 1 and 4 days after the day of
tumor inoculation showed significantly higher survival rates compared with those receiving PEG
liposomes without Tf, bare
liposomes or free
cisplatin solution. These results suggest that
cisplatin-encapsulated Tf-PEG
liposomes may be useful as a new intracellular targeting carrier for treatment of
gastric cancer with peritoneal dissemination.