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

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 (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.

journal_name

J Drug Target

authors

Tanaka S,Akaike T,Wu J,Fang J,Sawa T,Ogawa M,Beppu T,Maeda H

doi

10.1080/1061186031000086072

keywords:

subject

Has Abstract

pub_date

2003-01-01 00:00:00

pages

45-52

issue

1

eissn

1061-186X

issn

1029-2330

journal_volume

11

pub_type

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