Toward a full understanding of the EPR effect in primary and metastatic tumors as well as issues related to its heterogeneity

Adv Drug Deliv Rev. 2015 Aug 30;91:3-6. doi: 10.1016/j.addr.2015.01.002. Epub 2015 Jan 9.


The enhanced permeability and retention (EPR) effect of solid tumors as seen with nanomedicines and macromolecular drugs is well known. However, many researchers appear to lack a full understanding of this effect. The effect varies depending on a patient's pathological and physiological characteristics and clinical condition. When a patient's systolic blood pressure is low side of about 90mmHg instead of 120-130mmHg, the hydrodynamic force pushing blood from the luminal side of a vessel into tumor tissue becomes significantly low, which results in a low EPR. Also, a vascular embolism in a tumor may impede blood flow and the EPR. Here, I describe the background of the EPR effect, heterogeneity of this effect, physiological and pathological factors affecting the effect, the EPR effect in metastatic tumors, artifacts of the EPR effect with micellar and liposomal drugs, problems of macromolecular drug stability and drug release, and access to target sites.

Keywords: Anticancer drugs; EPR effect artifacts; EPR effect dependence on time and molecular size; EPR effect dynamics; Macromolecular drugs; Nanomedicines.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Drug Delivery Systems*
  • Drug Liberation
  • Humans
  • Liposomes
  • Macromolecular Substances / administration & dosage
  • Macromolecular Substances / pharmacokinetics
  • Micelles
  • Nanomedicine
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Permeability


  • Antineoplastic Agents
  • Liposomes
  • Macromolecular Substances
  • Micelles