ABSTRACT
A procedure has been developed for the preparation of large (10- to 80-microns-diameter) multivesicular liposomes that contain magnetic resonance contrast agent (DTPA and either manganese or gadolinium). Blue dextran was observed to induce the formation of the large liposomes with dioleoylphosphatidylcholine and cholesterol (1:1 molar ratio) and with dipalmitoylphosphatidylcholine and cholesterol (1:1 molar ratio). The formation of the large liposomes is dependent upon mixing the blue dextran with the lipid films at temperatures above the transition point of the lipids. Tracer amounts of 153Gd were added to the aqueous phase to permit quantitation of the recovery of encapsulated materials. Liposomes that were prepared using equimolar ratios of phospholipid and cholesterol were stable in serum for more than 12 h. The ultrastructure of the large multivesicular liposomes reveals the existence of individual vesicles (greater than 2 micron diameter) bound together by a multilamellar coating. When injected into the internal carotid artery of the rabbit, the large liposomes became entrapped in the vascular bed primarily in the frontal and occipital regions of brain. The resulting emboli may provide a means to deliver drugs to a specific site in brain, such as a tumor, if the vascular bed of the site can be cannulated precisely.