PMID- 20441782
OWN - NLM
STAT- MEDLINE
DCOM- 20111012
LR  - 20231120
IS  - 1872-8294 (Electronic)
IS  - 0169-409X (Linking)
VI  - 63
IP  - 3
DP  - 2011 Mar 18
TI  - The EPR effect: Unique features of tumor blood vessels for drug delivery, factors 
      involved, and limitations and augmentation of the effect.
PG  - 136-51
LID - 10.1016/j.addr.2010.04.009 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Fang, Jun
AU  - Fang J
AD  - Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo 
      University, Kumamoto, Japan.
FAU - Nakamura, Hideaki
AU  - Nakamura H
FAU - Maeda, Hiroshi
AU  - Maeda H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20100502
PL  - Netherlands
TA  - Adv Drug Deliv Rev
JT  - Advanced drug delivery reviews
JID - 8710523
SB  - IM
MH  - Animals
MH  - Capillary Permeability/drug effects/*physiology
MH  - Drug Delivery Systems/*methods
MH  - Extravasation of Diagnostic and Therapeutic 
      Materials/metabolism/pathology/*physiopathology
MH  - Humans
MH  - Neoplasms/*blood supply/*drug therapy/pathology/physiopathology
EDAT- 2010/05/06 06:00
MHDA- 2011/10/13 06:00
CRDT- 2010/05/06 06:00
PHST- 2010/03/30 00:00 [received]
PHST- 2010/04/26 00:00 [revised]
PHST- 2010/04/27 00:00 [accepted]
PHST- 2010/05/06 06:00 [entrez]
PHST- 2010/05/06 06:00 [pubmed]
PHST- 2011/10/13 06:00 [medline]
AID - S0169-409X(10)00090-6 [pii]
AID - 10.1016/j.addr.2010.04.009 [doi]
PST - ppublish
SO  - Adv Drug Deliv Rev. 2011 Mar 18;63(3):136-51. doi: 10.1016/j.addr.2010.04.009. 
      Epub 2010 May 2.