title: 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.
authors.affiliation: Department of Microbiology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Tanaka
authors.forename: Takaaki
authors.initials: T
authors.lastname: Akaike
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Sawa
authors.forename: Michio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Toru
authors.initials: T
authors.lastname: Beppu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maeda
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems / Q000379:methods; D011464:Epoprostenol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C048081:beraprost; D011464:Epoprostenol