DDS in cancer chemotherapy

Abstract

Despite the development of numerous anticancer agents, solid tumors in general respond poorly to chemotherapy. An objective of DDS in cancer chemotherapy is to find methods by which anticancer agents selectively target solid tumors. Two main concepts constitute selective tumor targeting, active targeting and passive targeting. The former involves monoclonal antibodies or ligands to tumor related receptors which can target the tumor by utilizing specific binding ability between the antibody and antigen or between the ligand and its receptor. The latter system can be achieved by the so-called “EPR effect, the enhanced permeability and retention effect”. The EPR effect in solid tumor tissue was named according to the pathophysiological characteristics : (a) hypervasculature ; (b) incomplete vascular architecture ; (c) several vascular permeability factors stimulating extravasation within the cancer ; (d) little drainage of macromolecules and particulates. Macromolecules have long plasma half-lives because they are too large to pass through the normal vessel walls unless they are trapped by the reticuloendothelial system in various organs. Such macromolecular agents can diffuse out of tumor blood vessels, reach the solid tumor tissue effectively and be retained for a long period due to the EPR effect. A DDS development technique enabled intravenous administration of water-insoluble drugs without using organic solvents which are usually vital to dissolve such hydrophobic drugs but have toxic effects. I review here recent clinical studies for DDS and introduce our recent work on the micelle system. © 1999, THE JAPAN SOCIETY OF DRUG DELIVERY SYSTEM. All rights reserved.