Modulation of tumor-selective vascular blood flow and extravasation by the stable prostaglandin 12 analogue beraprost sodium

J Drug Target. 2003 Jan;11(1):45-52. doi: 10.1080/1061186031000086072.


Improved delivery of macromolecular drugs to solid tumor is known as the enhanced permeability and retention (EPR) effect of macromolecular drugs and lipids. We report here that a prostaglandin I2 (PGI2) analogue induces enhancement of tumor-selective drug delivery, while it decreases tumor blood flow, in a rat tumor model (AH136B). Beraprost sodium (BPS) is an analogue of PGI2 that is more stable than parental PGI2 in vivo (t1/2 for BPS is > 1 h vs. a few seconds for PGI2). Thus, BPS was administered to tumor-bearing rats to examine its effect on tumor vascular permeability as well as tumor blood flow. The amount of extravasation of the Evans blue-albumin complex in tumor tissue increased from two to three times, whereas tumor blood flow decreased almost 70%, in the group treated with BPS at 7 (microg/kg compared with controls. Tissue blood flow of normal organs such as the kidney and the liver did not change to a significant extent. These findings establish a new role for BPS, not only in enhancing macromolecular drug delivery, but also in reducing the blood supply to tumor tissues.

MeSH terms

  • Animals
  • Capillary Permeability / drug effects*
  • Capillary Permeability / physiology
  • Drug Delivery Systems / methods
  • Epoprostenol / administration & dosage*
  • Epoprostenol / analogs & derivatives*
  • Epoprostenol / chemistry
  • Epoprostenol / pharmacokinetics
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Rats
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays / methods


  • beraprost
  • Epoprostenol