Intraperitoneal (i.p)
chemotherapy is an attractive approach to treat peritoneally disseminated
cancers by delivering therapeutic agents directly to the peritoneal cavity where some disseminated
tumors are located. Cationic
liposomes (CLs) have been used as a viable delivery carrier for i.p.
chemotherapy to improve the peritoneal retention of
anticancer agents. However, there are no reports on the fate of CLs following i.p. administration to the peritoneal cavity in the presence of disseminated
tumors. We prepared a
tumor xenograft murine model of peritoneally disseminated
gastric cancer by i.p. inoculation of human
gastric cancer cells and followed the fate of either CLs or PEGylated CLs (PEG-CLs) after i.p. injection in the model. I.p.-injected CLs were retained in peritoneal cavity for at least 3 days post-injection as a result of clustering with
ascites fluid
proteins, mainly
albumin, while i.p. PEG-CLs was rapidly cleared from the peritoneal cavity to the circulation within 3 h post-injection. Importantly, i.p. CLs efficiently accumulated in the targeted disseminated
tumor cells, but not in other abdominal organs including liver, spleen, and kidney. The
tumor selectivity upon i.p. administration of CLs may be associated with the lymphatic drainage system. A lipoplex formulation composed of CLs with
short hairpin RNA (
shRNA) against
luciferase, a model therapeutic agent, suppressed
luciferase activity in peritoneally disseminated
tumors by 80%, with no
cytokine secretion in serum. This suggests that i.p. CLs can efficiently deliver a therapeutic agent to peritoneally disseminated
tumors with few systemic adverse events. These results suggest that i.p. treatment with CLs or non-PEGylated lipoplexes may be a promising approach for the treatment of peritoneally disseminated
cancers through their ability to selectively deliver therapeutic agents to i.p. target sites with minimal systemic adverse events.