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 Targetjournal_title
Journal of drug targetingauthors
Tanaka S,Akaike T,Wu J,Fang J,Sawa T,Ogawa M,Beppu T,Maeda Hdoi
10.1080/1061186031000086072keywords:
subject
Has Abstractpub_date
2003-01-01 00:00:00pages
45-52issue
1eissn
1061-186Xissn
1029-2330journal_volume
11pub_type
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journal_title:Journal of drug targeting
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