Hepatic uptake and degradation of unilamellar sphingomyelin/cholesterol liposomes: a kinetic study.

The kinetics of hepatic uptake and degradation of sphingomyelin/cholesterol (2:1, M/M) small unilamellar liposomes were investigated in a BALB/c mouse. The tissue distribution of liposomes was determined by scintillation spectrometry. The percentage of intact liposomes in tissues was estimated by the technique of gamma-ray perturbed angular correlation. A kinetic model was developed to analyze the above data. A remarkable agreement was noted between the experimental data and the corresponding theoretical values. Our results indicate that the sphingomyelin/cholesterol unilamellar liposomes had an unusually long half-life of 16.5 hr in the circulation after intravenous administration to mice. The hepatic degradation of the liposomes in vitro at 37 degrees C followed first-order kinetics, with a half-life of 3.5 +/- 0.2 (SEM) hr. Furthermore, the rate of the in vivo degradation of liposomes in the liver was found to be quite similar to that in vitro, with a half-life of 3.6 +/- 0.4 hr. The rate of release of the liposome-encapsulated agent, indium-111, in the liver was not constant, and reached a maximum at about 8 hr after the administration of liposomes. The approach developed in the present study is general and can be applied to the investigation of factors that may control the release of pharmacologically active agents in any tissue.