RATES OF SYSTEMIC DEGRADATION AND RETICULOENDOTHELIAL SYSTEM (RES) UPTAKE OF THERMOSENSITIVE LIPOSOME ENCAPSULATING CISPLATIN IN RATS

The systemic degradation and reticuloendothelial system (RES) uptake o f cisplatin (CDDP)-encapsulated thermosensitive liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and, distearoylphosphatidylcholi ne (DSPC) (DPPC/DSPC = 9/1, 7/3, and 5/5, w/w) after intravenous admin istration to rats were examined by measuring the platinum (Pt) levels in the blood and RES (liver and spleen). The blood liposome level prof ile showed first-order rate elimination for each liposome administrati on. The elimination rate (K(el)) was faster when the content of DSPC w as lower (K(el): 1.3/hr for 9/1-liposomes, 0.7/hr for 7/3-liposomes, 0 .5/hr for 5/5-liposomes). On the other hand, the RES liposome level pr ofile showed distribution of liposomes followed by elimination therefr om. 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 analys is demonstrated that the RES uptake rate (K(res)) was almost the same among the liposomes (0.4/hr), while the systemic degradation rate (K(d eg); K(el) - 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 lip osome degradation. The K(deg) for each type of liposome corresponded w ith the systemic CDDP release rate.