Rates of Systemic Degradation and Reticuloendothelial System (RES) Uptake of Thermosensitive Liposome Encapsulating Cisplatin in Rats

Abstract

The systemic degradation and reticuloendothelial system (RES) uptake of cisplatin (CDDP)-encapsulated thermosensitive liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and di-stearoylphosphatidylcholine (DSPC) (DPPC/DSPC = 9/1, 7/3, and 5/5, w/w) after intravenous administration to rats were examined by measuring the platinum (Pt) levels in the blood and RES (liver and spleen). The blood liposome level profile showed first-order rate elimination for each liposome administration. The elimination rate (K _e1) was faster when the content of DSPC was lower (K _e1: 1.3/hr for 9/1-liposomes, 0.7/hr for 7/3-liposomes, 0.5/hrfor5/5-liposomes). On the other hand, the RES liposome level profile showed distribution of liposomes followed by elimination therefrom. The RES level of the liposomes was lower when the content of DSPC was smaller (maximal level: 25% for 9/1-liposomes at 1 hr, 32% for 7/3-liposomes at 1 hr, 37% for 5/5-liposomes at 2 hr). The kinetic analysis demonstrated that the RES uptake rate (K _res) was almost the same among the liposomes (0.4/hr), while the systemic degradation rate (K _deg; K _e1 − K _res) became larger as the content of DSPC decreased (0.9/hr for 9/1-liposomes, 0.3/hr for 7/3-liposomes, and 0.1/hr for 5/5-liposomes) and that the RES liposome distribution amount was dependent not only on the K _res but also on the K _deg and the rate of RES liposome degradation. The K _deg for each type of liposome corresponded with the systemic CDDP release rate.