Studies on the Uptake Mechanism of Liposomes by Perfused Rat Liver. II. An Indispensable Factor for Liver Uptake in Serum

Abstract

Participating factors in the uptake of liposomes by the liver were examined in a small-volume circulating perfusion system. The volume of the perfusate was 23 ml, which corresponds to the blood volume of the rat. It is considered that this system is suitable for examining the factors participating in the uptake in vivo. An indispensable factor for the uptake was found in fresh serum, and the uptake proportionally depended on the amount of the factor in serum. The properties of the factor were investigated with serum pretreated in various ways. The experiment with preheated serum indicated that the factor is very heat-sensitive and may be a protein. When serum was dialyzed with a cellulose membrane, the activity penetrated through the membrane, and its molecular weight was concluded to be below 17000 daltons. The sum of the activities on both sides of the membrane in equilibrium dialysis was also equal to that in fresh serum. This strongly suggests that the factor does not participate cooperatively with other factors in the uptake. The uptake activity disappeared when serum was incubated with liposomes at 38.degree. C for 5 min in advance. The interaction of the factor with liposomes appears to be very fast and irreversible. Correspondence of the uptake by the liver and elimination from the perfusate in the perfusion system to the in vivo behavior after i.v. injection was also examined. Correspondence of the uptake was observed, but the elimination kinetics from perfusate and blood were different. It is suggested that the uptake is dominated by the factor described here, but the elimination kinetics is partially affected by other factor(s).