Liposome disposition in vivo II: Dose dependency.

The dose-dependent disposition of extruded multilamellar (diameter approximately 1 micrometer) negatively charged liposomes containing entrapped [14C]inulin was studied in mice. Mice received 1500, 300, or 15 mumoles of liposomal lipid/kg iv. Carbon 14 levels were measured in the blood, liver, spleen, and carcass for 72 hr. A pronounced saturation effect, consistent with the known dose behavior of other colloids, was seen at early times; it was manifested by higher dose values in the blood and spleen but by lower liver values as the dose increased. This dose effect was attenuated in the liver but was maintained in the spleen at later times, and percent dose values approached plateau values in all tissues for all doses at later times. [14C]Inulin was used at the liposomal marker because of its inability to enter cells (or, presumably, leave them if delivered there by liposomes) in its free form. An early decline in carbon 14 levels (over the first 48 hr) was seen in the liver for the low and medium doses. Because of the known ability of blood factors to cause liposomes to leak their contents, this decline was interpreted as being a loss of [14C]inulin from extracellularly bound liposomes during this period. Moreover, the plateau carbon 14 levels at later times were interpreted as approximating the true level of intracellular inulin delivery by the liposomes.