Decreased binding affinity of apolipoprotein E plays an important role in the reduced hepatic clearance of Lipid Nano-Sphere (LNS)

Abstract

We have shown that a lipid nanoparticle, Lipid Nano-Sphere (LNS), with a diameter of 25-50 nm, showed a prolonged plasma half-life of an incorporating drug in comparison with a conventional fat emulsion, Lipid Microsphere (LM), with a diameter of 200-300 nm, and this was due to the difference in their hepatic clearances. LM showed an elevated plasma profile in rats pretreated with lactoferrin which blocks the receptors for apo E on liver cells. The liver uptake of LM in normal rats was decreased markedly when rats were treated with lactoferrin. On the other hand, the lactoferrin pretreatment affected neither the plasma profile nor the hepatic clearance obtained with LNS. Apo E was hardly associated with LNS. The dissociation constant of LNS to endogenous apo E in human serum was 50-fold greater than that of LM. From these results, it was suggested that apo E recognize their particle sizes of exogenous lipid particles and regulate their hepatic clearances in a size-dependent manner.