Studies on the uptake mechanism of liposomes by perfused rat liver. I. An investigation of effluent profiles with perfusate containing no blood component.

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Abstract
Uptake of liposomes by perfused rat liver was examined, and the effluent profiles are discussed. Reverse-phase evaporation vesicles (REV, about 0.1-0.2 .mu.m in diameter) were able to pass through the liver without any interaction or interference and there was little uptake by the liver during single perfusion with phosphate-buffered saline. The transit time of REV was shorter than that of inulin simultaneously injected as a flow marker. These results suggest that the uptake of REV by the liver requires opsonization by blood components, and if REV can escape opsonization, they may be able to pass through the liver freely. It is also clear that the distribution volume of the REV is smaller than that of inulin. On the other hand, small unilamellar vesicles (SUV, about 0.06 .mu.m in diameter) showed uptake corresponding to about 0.25 .mu.mol of total lipid without any participation of blood components. This result suggests that the uptake mechanism of SUV may be different from that of REV, and opsonization may not be essential for the uptake of SUV by the liver. A comparison of the results for REV and SUV suggests that the functional pore size of the fenestration of liver sinusoids is about 0.06 .mu.m, and about half of the SUV prepared in this study could pass through the fenestration and reach the hepatocytes, while the other part of the SUV drained through the liver as did REV. The uptake of SUV by the liver seemed to be limited in capacity, and it was influenced by temperature and inhibited by predosing with liposomes containing sodium azide or cytochalasin B.

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