Translymphatic chemotherapy targeting sentinel lymph nodes using a novel phospholipid polymer-Paclitaxel conjugate

Anticancer Res. 2014 Apr;34(4):1751-7.

Abstract

Background: Although sentinel node (SN) biopsy has been applied for various types of solid tumors, its clinical significance is currently limited to the field of diagnostics. We developed a new translymphatic chemotherapy approach using a novel phospholipid polymer (PMB30W), which facilitates the dissolution of large amounts of paclitaxel. The purpose of the present study was to investigate the pharmacokinetics and antitumor effect of this conjugate (PTX-PMB30W) in a rat model.

Materials and methods: PTX-PMB30W was directly administered into the cecal submucosa or through the tail vein. The antitumor effect was compared between the two groups.

Results: Paclitaxel concentrations in SNs remained constant over a 24-h period after local administration. Tumor growth was clearly suppressed by submucosal administration of PTX-PMB30W, resulting in a survival benefit compared to intravenous administration.

Conclusion: Translymphatic chemotherapy targeting SNs via direct administration of PTX-PMB30W appears feasible, and this strategy may be applicable to the multi-disciplinary management of early solid cancer.

Keywords: 2-methacryloyloxyethyl phosphorylcholine; Translymphatic chemotherapy; micrometastasis; paclitaxel; sentinel node.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Body Weight
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Inhibitory Concentration 50
  • Lymph Nodes / drug effects*
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Male
  • Methacrylates* / administration & dosage
  • Methacrylates* / chemistry
  • Neoplasms / drug therapy*
  • Neoplasms / mortality
  • Neoplasms / pathology*
  • Paclitaxel / administration & dosage*
  • Paclitaxel / chemistry
  • Paclitaxel / toxicity
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemistry
  • Rats
  • Sentinel Lymph Node Biopsy

Substances

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