Kinetic study on the optimization of tumor delivery of antitumor agents by liposomes :

Simulation study based on the physiological modeling

Abstract

We have developed a physiological model for free and liposomal DOX to calculate the time course of free DOX in extracellular space of tumor tissue and to calculate area under the curve as an index of antitumor effect of doxorubicin. Simulations were performed to clarify the relationship between antitumor effect and pharmacokinetic or physicochemical parameters of liposomes under different physiological conditions of tumor tissues. The importance of long circulation time of liposomes was confirmed and the optimum rate of drug release from long circulating liposomes was found to depend on tumor sensitivity to the antitumor agent. This simulation can provide useful information in development of optimized drug carrier for antitumor agents.