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

Cancer Sci. 2009 Oct;100(10):1979-85. doi: 10.1111/j.1349-7006.2009.01265.x. Epub 2009 Jun 26.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Drug Carriers / administration & dosage*
  • Drug Carriers / pharmacokinetics
  • Female
  • Humans
  • Injections, Intraperitoneal
  • Methacrylates / administration & dosage*
  • Methacrylates / pharmacokinetics
  • Mice
  • Mice, Nude
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / secondary
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / pharmacokinetics
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / pathology
  • Tissue Distribution
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Drug Carriers
  • Methacrylates
  • Phosphorylcholine
  • poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate)
  • Paclitaxel