Tissue Distribution and Pharmacokinetic Evaluation of the Targeting Efficiency of Synthetic Alkyl Glycoside Vesicles

抄録

The tissue distribution of alkyl glycoside vesicles (AGV), which are based on synthetic alkyl glycosides, was examined after intravenous administration in mice, and the results were compared with those for phosphatidylcholine liposomes (PC liposomes). Two types of AGV were used in this study, i.e., vesicles based on stearyl galactoside (Gal-ST vesicles) and stearyl glucoside (Glu-ST vesicles). The Gal-ST vesicles showed significantly higher accumulation in the liver compared with the Glu-ST vesicles and PC liposomes, and this high accumulation was maintained for a long time (8h). On the other hand, the Gal-ST vesicles and the Glu-ST vesicles showed lower accumulation in the spleen than PC liposomes. It appears that galactoside vesicles have an affinity for the liver and the AGV intrinsically have a lower affinity for the spleen than PC liposomes. Targeting of galactoside vesicles to the liver was expected. In order to evaluate the tissue distribution profiles quantitatively, pharmacokinetic analysis of the time course data was carried out based on a physiological flow model. It has become apparent in this analysis that the affinity of the Gal-ST vesicles for the liver was as high as 1.5 times those of Glu-ST vesicles and PC liposomes, while those of Gal-ST vesicles and Glu-ST vesicles for the spleen were about a half of that of PC liposomes. It also appears that the degradation rate of these vesicles in the tissues differs with different types of vesicles. Such an analysis leading to quantitative evaluation of the targeting efficiency should be useful for developing vesicles as drug carriers.