Open AccessSpatial distribution of intraperitoneally administrated paclitaxel nanoparticles solubilized with poly (2‐methacryloxyethyl phosphorylcholine‐co n‐ butyl methacrylate) in peritoneal metastatic nodules
Author(s) -
Kamei Takao,
Kitayama Joji,
Yamaguchi Hironori,
Soma Daisuke,
Emoto Shigenobu,
Konno Tomohiro,
Ishihara Kazuhiko,
Ishigami Hironori,
Kaisaki Shoichi,
Nagawa Hirokazu
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2010.01747.x
Subject(s) - paclitaxel , medicine , phosphorylcholine , metastasis , infiltration (hvac) , chemotherapy , pharmacology , cancer research , pathology , cancer , chemistry , biochemistry , materials science , composite material
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. ( Cancer Sci 2011; 102: 200–205)