微粒子製剤設計とDDS

血中滞留性リポソームによる抗癌剤の処方設計における最適化

抄録

Development of long circulating liposomes (LCL) has become a break through in establishing a drug delivery system using liposomes for antitumor agents. In this study, we have constructed a pharmacokinetic/pharmacodynaniic (PK/PD)-model for doxorubicin (DOX) in mice to analyze the optimum conditions of LCL. Simulation analysis revealed that there existed the optimum release rate of DOX from LCL with a half life approximately 10 hs, regardless of tumor growth rate or tumor sensitivity to DOX. Then, we have tested our PK/PD-model by in vivo survival experiments, which has shown validity of our model. We have also scaled-up the PK/PD-model from mice to humans by substitution of PR parameters for free DOX and LCL. In our preliminary simulations, it was suggested that the optimum release rate of DOX was depended on tumor growth rate as well as tumor sensitivity to DOX, which was different in the case of mice. This PK/PD-modeling will become a useful strategy when we optimize DDS.