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

Abstract

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. The sphingomyelin/cholesterol unilamellar liposomes had an unusually long half-life (t1/2) of 16.5 h in the circulation after i.v. administration to mice. The hepatic degradation of the liposomes in vitro at 37.degree. C followed 1st-order kinetics, with a t1/2 of 3.5 .+-. 0.2 (SEM [SE of mean]) h. The rate of the in vivo degradation of liposomes in the liver was similar to that in vitro, with a t1/2 of 3.6 .+-. 0.4 h. The rate of release of the liposome-encapsulated agent, indium-111, in the liver was not constant, and reached a maximum at .apprx. 8 h 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.