K. Iga et al., RATES OF SYSTEMIC DEGRADATION AND RETICULOENDOTHELIAL SYSTEM (RES) UPTAKE OF THERMOSENSITIVE LIPOSOME ENCAPSULATING CISPLATIN IN RATS, Pharmaceutical research, 10(9), 1993, pp. 1332-1337
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.