Decreased binding affinity of apolipoprotein C-II to Lipid Nano-Sphere (LNS) plays an important role in the plasma half-life and reduced hæmolytic activity

Abstract

A lipid nanoparticle, Lipid Nano-Sphere (LNS), with a diameter of 25–50nm, showed a prolonged plasma half-life of an incorporating drug in comparison with a conventional lipid emulsion, Lipid Microsphere (LM), with a diameter of 200–300nm. LM showed an elevated plasma profile in rats pretreated with Triton WR-1339 which blocks lipolysis by lipoprotein lipase. Triton WR-1339 did not affect the plasma profile of LNS. It was showed that apo C-II bound to LM with much higher affinity than to LNS. The dissociation constants of the lipid particles for apo C-II in human serum were 70-fold as much greater than for apo E. Hæmolysis with elevated plasma lysophosphatidylcholine levels was found in rats that received bolus injection of LM. But LNS did not cause hæmolysis. From these results, it was suggested that apo C-II recognized their particle size of lipid particles and played a key role in their plasma half-lives.