Passive vs. Active Targeting: An Update of the EPR Role in Drug Delivery to Tumors

Abstract

A variety of active pharmaceutical ingredients (APIs) currently used for cancer treatment are cytotoxic, and show nonspecific distribution when administered systemically resulting in toxicity to normal tissues, hence limiting their clinical application. To overcome these challenges, nanocarriers such as liposomes and micelles have been widely used to deliver APIs for cancer chemotherapy. Delivery of nanocarriers is achieved either via “passive targeting” owing to the enhanced permeability and retention (EPR) effect or via “active targeting” due to the presence of various ligands on the surface of nanocarriers, such as antibodies, peptides, etc. Numerous factors are involved in successful delivery of chemotherapeutic agents; these depend on the tumor microenvironment, formulation factors such as choice of ligand use, physiochemical properties of the nanocarriers, and the choice of target. In this chapter, we discuss the fundamentals of EPR effect, factors affecting passive and active targeting, and current clinical update of various actively and passively targeted liposomes and micelles.