The EPR effect: Its history, development and future implication

Abstract

I have described herein the history, and controversial issues of the EPR (enhanced permeability and retention) effect, including various factors involved, heterogeneity, genetic mutational diversity, obstacles to the tumor blood flow or thrombi formation, and counter measures to overcome these problems in the EPR-based drug delivery. Also gaps between experimental models of mice, in contrast to practical human clinical setting are discussed. Issues of cell internalization, which is greatly affected by the nature of active pharmaceutical ingredient (API) was demonstrated using HPMA polymer(P)-conjugated-pirarubicin (THP) and P-doxorubicin, where there is more than 30 fold difference with P-THP being superior. Critical Importance of the enhancers of the EPR effect such as nitroglycerin is also described.