KINETIC MODELING OF LIPOSOME DEGRADATION IN BLOOD-CIRCULATION

The aim of this study is to develop a kinetic model for the quantitative evaluation of, and to examine dose dependency in liposome degradation in blood circulation in vivo. Multilamellar liposomes labeled with H-3-inulin were administered intravenously into rats and the time courses of blood concentration and urinary excretion of H-3-inulin were measured. The dosages of liposomes were fixed at 1, 5, and 100 mumolPCkg-1. Remarkable saturation was found in the time courses of both blood concentration and urinary excretion. Then a kinetic model for the degradation of liposomes in blood was developed, assuming that the degradation follows the first order rate process for each dose. The model fitted the observed time courses of excreted H-3-inulin well, and dose dependency could be observed in the rate constants for liposome degradation, which are more sensitive than urinary excretion of H-3-inulin. The degradation rate constant correlated well with the uptake rate constant, which suggests the same underlying mechanism for both uptake and degradation. These results indicate the usefulness of kinetic modeling in the quantitative evaluation of liposome degradation in blood circulation in vivo.