Intraperitoneal (i.p.) administration of
paclitaxel nanoparticles (PTX-30W) prepared by solubulization with the amphiphilic copolymer of 2-methacryloxyethyl
phosphorylcholine and n-
butyl methacrylate can efficiently suppress the growth of peritoneal
metastasis. In this study, we characterized the
drug distribution of i.p. injected PTX-30W in peritoneal
tumor and liver in a mouse model using MKN45, human
gastric cancer cells. Oregon green-conjugated PTX-30W showed perivascular accumulation in MKN45
tumor in the peritoneum at 24 h after intravenous (i.v.) injection; however, the amount of PTX in
tumor was markedly less than that in liver. In contrast, a larger amount of PTX accumulated in the peripheral area of disseminated nodules at 1 h after i.p. injection and the area gradually enlarged. The depth of PTX infiltration reached 1 mm from the
tumor surface at 48 h after i.p. injection, and the fluorescence intensity was markedly greater than that in liver. Interestingly, i.p. injected PTX preferentially accumulated in relatively hypovascular areas, and many
tumor cells in the vicinity of PTX accumulation showed apoptosis. This unique accumulation pattern and lesser washout in hypovascular areas are thought to be attributable to the superior penetrating activity of PTX-30W, and thus, PTX-30W is considered to be highly suitable for i.p.
chemotherapy for peritoneal dissemination.