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The EPR effect: Unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect.
- Source :
-
Advanced drug delivery reviews [Adv Drug Deliv Rev] 2011 Mar 18; Vol. 63 (3), pp. 136-51. Date of Electronic Publication: 2010 May 02. - Publication Year :
- 2011
-
Abstract
- The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors related to their anatomical and pathophysiological differences from normal tissues. For example, angiogenesis leads to high vascular density in solid tumors, large gaps exist between endothelial cells in tumor blood vessels, and tumor tissues show selective extravasation and retention of macromolecular drugs. This EPR effect served as a basis for development of macromolecular anticancer therapy. We demonstrated methods to enhance this effect artificially in clinical settings. Of great importance was increasing systolic blood pressure via slow angiotensin II infusion. Another strategy involved utilization of NO-releasing agents such as topical nitroglycerin, which releases nitrite. Nitrite is converted to NO more selectively in the tumor tissues, which leads to a significantly increased EPR effect and enhanced antitumor drug effects as well. This review discusses molecular mechanisms of factors related to the EPR effect, the unique anatomy of tumor vessels, limitations and techniques to avoid such limitations, augmenting tumor drug delivery, and experimental and clinical findings.<br /> (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Capillary Permeability drug effects
Extravasation of Diagnostic and Therapeutic Materials metabolism
Extravasation of Diagnostic and Therapeutic Materials pathology
Humans
Neoplasms pathology
Neoplasms physiopathology
Capillary Permeability physiology
Drug Delivery Systems methods
Extravasation of Diagnostic and Therapeutic Materials physiopathology
Neoplasms blood supply
Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8294
- Volume :
- 63
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Advanced drug delivery reviews
- Publication Type :
- Academic Journal
- Accession number :
- 20441782
- Full Text :
- https://doi.org/10.1016/j.addr.2010.04.009