Pharmacological disposition of negatively charged phospholipid vesicles in rats.

The pharmacological disposition of four negatively charged phospholipid vesicles with radioactive cholesteryl oleate as a tracer was investigated in rats. The acidic phospholipids included phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and diphosphatidylglycerol (cardiolipin). The blood half-life of phosphatidylserine vesicles was the shortest (< 2 min), while that of phosphatidylinositol was the longest (90 min). Cardiolipin and phosphatidylglycerol vesicles had intermediate blood half-lives (7 and 18 min, respectively). The distribution of these vesicles in six major organs (liver, spleen, heart, kidneys, lungs, and brain) varied greatly. Contrary to the long-held belief, it was possible to prepare negatively charged phospholipid vesicles with long blood half-lives. Furthermore, tissue disposition of these negatively charged vesicles could be manipulated partially by judicious selection of their components.