Applying Models of Targeted Drug Delivery to Gene Delivery

Gene delivery requires targeted delivery systems. Exploratory simulations using models of targeted drug delivery helps one assess the worthiness of such systems, and helps quantify the expected therapeutic benefits of the systems. The drug targeting index (DTI), a ratio of availabilities, is a measure of pharmacokinetic benefit of the delivery device, based on a combination of a physiologically-based pharmacokinetic model and a single pharmacodynamic Emaxmodel. Pharmacodynamic outcomes are quantified by the degree of separation between the dose-response and dose-toxicity curves (SRT). Simulations are undertaken to investigate the potential linkage of DTI and SRT, a pharmacodynamic outcome. A significant positive linear relationship is found between the DTI and SRT. The relationship can be translated into a minimum pharmacokinetic requirement that can be used to guide making decisions regarding whether or not further pursue the development of a candidate gene-delivery device as a therapeutic agent.