Application of Mixture Designs for Detection and Characterization of Multi-Drug Synergism

Detection and characterization of synergism are critical focus in multi-drug interplay. To assess combined drug action, the classical methods such as isobologram and interaction index are still simple and sometimes unable to describe complex drug interaction adequately. Statistical-model based methods are found more flexible and informative in detecting and characterizing complex drug interactions, which require well- designed experiments. In this study, a kind of experimental designs, called mixture designs, is proposed for the detection and characterization of multi-drug synergism and optimization. Compared with other statistical-model based methods, mixture designs are demonstrated to be more useful when the total dose of the drugs under investigation is to be controlled in a moderate level. A case study of inhibition effect of three bioactive chemical compounds identified from an anti-angiogenesis traditional Chinese medicine on human umbilical vein endothelial cells is shown as an illustration to demonstrate the application of mixture designs in multi-drug combination discovery.