Modulation of tumor-selective vascular blood flow and extravasation by the stable prostaglandin I2 analogue beraprost sodium

Shinichiro Tanaka, Takaaki Akaike, Jun Wu, Jun Fang, Tomohiro Sawa, Michio Ogawa, Toru Beppu, Hiroshi Maeda

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalJournal of Drug Targeting
Volume11
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1
Externally publishedYes

Keywords

  • Enhanced permeability
  • Modulation of EPR effect
  • Prostaglandin I analogue
  • Tumor delivery

ASJC Scopus subject areas

  • Pharmaceutical Science

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