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Intraperitoneal administration of paclitaxel solubilized with poly(2-methacryloxyethyl phosphorylcholine-co n-butyl methacrylate) for peritoneal dissemination of gastric cancer.

Abstract
Intraperitoneal (i.p.) administration of paclitaxel (PTX) is a hopeful therapeutic strategy for peritoneal malignancy. Intravenously (i.v.) injected nanoparticle anticancer drugs are known to be retained in the blood stream for a long time and favorably extravasated from vessels into the interstitium of tumor tissue. In this study, we evaluated the effect of i.p. injection of PTX (PTX-30W), which was prepared by solubulization with water-soluble amphiphilic polymer composed of PMB-30W, a co-polymer of 2-methacryloxyethyl phosphorylcholine and n-butyl methacrylate, for peritoneal dissemination of gastric cancer. In a peritoneal metastasis model with transfer of MKN45P in nude mice, the effect of i.p. administration of PTX-30W was compared with conventional PTX dissolved in Cremophor EL (PTX-Cre). The drug accumulation in peritoneal nodules was evaluated with intratumor PTX concentration and fluorescence microscopic observation. PTX-30W reduced the number of metastatic nodules and tumor volume significantly more than did conventional PTX dissolved in Cremophor EL (PTX-Cre), and prolonged the survival time (P < 0.05). PTX concentration in disseminated tumors measured by HPLC was higher in the PTX-30W than in the PTX-Cre group up to 24 h after i.p. injection. Oregon green-conjugated PTX-30W, i.p. administered, preferentially accumulated in relatively hypovascular areas in the peripheral part of disseminated nodules, which was significantly greater than the accumulation of PTX-Cre. I.p. administration of PTX-30W may be a promising strategy for peritoneal dissemination, due to its superior characteristics to accumulate in peritoneal lesions.
AuthorsDaisuke Soma, Joji Kitayama, Tomohiro Konno, Kazuhiko Ishihara, Jun Yamada, Takao Kamei, Hironori Ishigami, Shoichi Kaisaki, Hirokazu Nagawa
JournalCancer science (Cancer Sci) Vol. 100 Issue 10 Pg. 1979-85 (Oct 2009) ISSN: 1349-7006 [Electronic] England
PMID19604244 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antineoplastic Agents
  • Drug Carriers
  • Methacrylates
  • Phosphorylcholine
  • poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)
  • Paclitaxel
Topics
  • Animals
  • Antineoplastic Agents (administration & dosage, pharmacokinetics)
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Drug Carriers (administration & dosage, pharmacokinetics)
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Methacrylates (administration & dosage, pharmacokinetics)
  • Mice
  • Mice, Nude
  • Paclitaxel (administration & dosage, pharmacokinetics)
  • Peritoneal Neoplasms (drug therapy, secondary)
  • Phosphorylcholine (administration & dosage, analogs & derivatives, pharmacokinetics)
  • Stomach Neoplasms (drug therapy, pathology)
  • Tissue Distribution
  • Xenograft Model Antitumor Assays

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