Tumor vascular permeability and the EPR effect in macromolecular therapeutics: A review

H. Maeda, J. Wu, T. Sawa, Y. Matsumura, K. Hori

Research output: Contribution to journalArticlepeer-review

5252 Citations (Scopus)


Most solid tumors possess unique pathophysiological characteristics that are not observed in normal tissues or organs, such as extensive angiogenesis and hence hypervasculature, defective vascular architecture, impaired lymphatic drainage/recovery system, and greatly increased production of a number of permeability mediators. The phenomenon now known as the enhanced permeability and retention (EPR) effect for lipid and macromolecular agents has been observed to be universal in solid tumors. Primarily, enhanced vascular permeability will sustain an adequate supply of nutrients and oxygen for rapid tumor growth. The EPR effect also provides a great opportunity for more selective targeting of lipid- or polymer-conjugated anticancer drugs, such as SMANCS and PK-1, to the tumor. In the present review, the basic characteristics of the EPR effect, particularly the factors involved, are described, as well as its modulation for improving delivery of macromolecular drugs to the tumor. Tumor-specific vascular physiology is also described. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)271-284
Number of pages14
JournalJournal of Controlled Release
Issue number1-2
Publication statusPublished - 2000 Mar 1
Externally publishedYes


  • EPR effect
  • Macromolecular therapeutics
  • Permeability factors
  • Tumor targeting
  • Tumor vascular permeability

ASJC Scopus subject areas

  • Pharmaceutical Science


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