Sustained Delivery of an ApolipoproteinE Peptidomimetic Lowers Serum Cholesterol Levels in Dyslipidemic Mice

Receptor-mediated removal of LPs by the liver is predominantly mediated by apolipoproteinE. Recent data show that a novel dual domain peptide (hE-18A) containing the 10-residue receptor-binding domain of human apoE, and a model class A amphipathic helix (18A), can associate with low density and very low density lipoproteins (LDL, VLDL) and enhance their uptake and degradation by HepG2 cells; and further, causes a dramatic reduction in plasma cholesterol levels in apoE-null mice [1,2]. These results provide the basis for developing sustained-release vehicles for this novel peptide as an alternate form of treatment for hypercholesterolemia and hypertriglyceridemia. We encapsulated this peptide into a multivesicular liposome (MVL) depot-delivery system (DepoFoam™) [3], and evaluated its sustained-release properties in vitro and its pharmacodynamic effects in a dyslipidemic mouse model.