In vivo evaluation of the effect of the size and opsonization on the hepatic extraction of liposomes in rats: an application of Oldendorf method.

In the hepatic uptake of large particles such as liposomes, a serum component called opsonin plays an important role. In this study, the 'Oldendorf method' is introduced to evaluate the hepatic extraction under the condition of single passage, which enabled examination of the effect of opsonization on liposome uptake by the intact liver. 14C-labelled liposomes and, an internal reference, 3H-H2O were injected as a bolus into portal vein. Liver uptake index (LUI) was calculated from the ratio of the extraction of 14C to that of 3H. The effect of liposome size (mean diameter of 0.8, 0.4, 0.2, and 0.05 micron) and opsonization (preincubation with fresh blood for 5 min) on liposomal hepatic uptake were investigated using this method. LUI increased with size significantly (p < 0.001), and opsonization enhanced LUI only for the large liposomes (0.8 micron). This result suggests that the critical diameter of opsonization for these liposomes lies between 0.4 and 0.8 micron.