Kunio Higashi

Effects of sialic acid derivative on long circulation time and tumor concentration of liposomes

Abstract The effects of a sialic acid derivative, Neu5Aβ-PA, on the blood circulation and tissue distribution of liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol (Chol) and Neu5Aβ-PA were investigated compared with liposomes composed of DPPC, Chol and monosialoganglioside GM 1 , in mice and rats. When liposomes containing Neu5Aβ-PA were intravenously administered into mice, the plasma concentration of liposomes containing Neu5Ac/3-PA was increased, and the liver and spleen uptakes were decreased; there was no significant difference in tissue distribution between liposomes containing Neu5Aβ-PA (DPPC/Chol/Neu5Aβ-PA= 10: 10:3) and those containing GM 1 , (DPPC/Chol/GM 1 = 10:10:1). On the other hand, the plasma concentration of liposomes containing Neu5Aβ-PA was significantly greater than that of liposomes containing GM 1 , at all times determined in rats, and was about 30.7- and 10.3-fold that of liposomes containing GM 1 , at 6 and 24 h, respectively. The liver and spleen uptakes of liposomes containing Neu5Aβ-PA at 6 h were significantly reduced compared with those of liposomes containing GM, in rats. The tumor accumulation of liposomes was also examined. The liver/tumor ratio of liposomes containing Neu5Aβ-PA was similar to that of liposomes containing GM 1 in mice and lower than that of liposomes containing GM 1 in rats.