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Spatial distribution of intraperitoneally administrated paclitaxel nanoparticles solubilized with poly (2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) in peritoneal metastatic nodules.

Abstract
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.
AuthorsTakao Kamei, Joji Kitayama, Hironori Yamaguchi, Daisuke Soma, Shigenobu Emoto, Tomohiro Konno, Kazuhiko Ishihara, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
JournalCancer science (Cancer Sci) Vol. 102 Issue 1 Pg. 200-5 (Jan 2011) ISSN: 1349-7006 [Electronic] England
PMID20942868 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2010 Japanese Cancer Association.
Chemical References
  • Antineoplastic Agents, Phytogenic
  • Methacrylates
  • Phosphorylcholine
  • poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacokinetics)
  • Cell Line, Tumor
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Liver (metabolism)
  • Methacrylates (chemistry)
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles (administration & dosage)
  • Paclitaxel (administration & dosage, pharmacokinetics)
  • Peritoneal Neoplasms (drug therapy, metabolism, secondary)
  • Phosphorylcholine (analogs & derivatives, chemistry)
  • Solubility
  • Tissue Distribution

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