A clinical trial can determine the course of DDS development

Abstract

There are two main concepts in DDS, passive targeting and active targeting. The passive targeting system is achieved by the EPR effect, that is, the enhanced permeability and retention effect. Several DDS formulations have been approved worldwide. A phase 3 trial of a micelle formulation developed for the first time in Japan is now underway. Due to the success of T-DM1 in patients with metastatic breast cancer, active targeting, or antibody-drug conjugate (ADC), is again receiving attention in a robust fashion. but this ADC strategy should be confined to highly toxic anticancer agents but not to ordinary ACA such as taxane, adriamycin and others because only less than three ACA molecules should be conjugated to the mAb, otherwise the affinity of the mAb is diminished if too many molecules of ACA are attached to the mAb. According to this principle, unrealistic amount of ADC should be administered if the mAbs are conjugated with an ordinary ACA. Therefore, for an ordinary ACA, nanoparticles should be considered as a DDS tool. Investigators of DDS should keep in mind at an early stage of development what the target cancer is and what kind of regimen is the current standard therapy for future clinical evaluation.