Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors

Abstract

It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation kinetics, with an apparent K(m) of 13.1 ng protein/mL. LDE-apo is able to displace LDL uptake by mononuclear cells with a Ki of 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of 14C-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same receptor sites. In human hyperlipidemias, LDE labeled with 14C-cholesteryl ester behaved kinetically as expected for native LDL. LDE plasma disappearance curve obtained from eight hypercholesterolemic patients was markedly slower than that from 10 control normolipidemic subjects [fractional clearance rate (FCR) = 0.02 +/- 0.01 and 0.12 +/- 0.04 h-1, respectively; P < 0.0001]. On the other hand, in four severely hypertriglyceridemic patients, LDE FCR was not significantly different from the controls (0.07 +/- 0.03 h-1). These results suggest that LDE can be a useful device to study lipoprotein metabolism.

Nanoemulsions in Translational Research—Opportunities and Challenges in Targeted Cancer Therapy

“…For example, cholesterol-rich nanoemulsions (LDE) upon contact with plasma can acquire apo E and other apolipproteins from native lipoproteins and bind to low-density lipoprotein (LDL) or LDLrelated protein receptors (108). These receptors are highly expressed on cancer cells, and inclusion of cytotoxic agent can promote cancer cell-specific delivery (109).…”

Plasma kinetics of a cholesterol-rich emulsion in subjects with or without coronary artery disease

“…All these operational advantages greatly facilitate the execution of systematic studies on the plasma kinetics of lipids. Emulsion models of lymph chylomicrons have been used to clarify the chylomicron metabolism status in several disease states and the action of antilipidemic drugs upon this metabolism (6-10).The metabolism of LDL can also be probed with artificial emulsions (1)(2)(3)(4)(5)(11)(12)(13). In this regard, we have previously studied the metabolic behavior of a cholesterol-rich emulsion termed cholesterol rich emulsion (LDE) that roughly resembles the LDL lipidic structure.…”

“…The metabolism of LDL can also be probed with artificial emulsions (1)(2)(3)(4)(5)(11)(12)(13). In this regard, we have previously studied the metabolic behavior of a cholesterol-rich emulsion termed cholesterol rich emulsion (LDE) that roughly resembles the LDL lipidic structure.…”

“…Emulsions of defined composition resembling the lipidic structure of the plasma lipoproteins are a practical and efficient tool to investigate the lipid intravascular metabolism (1)(2)(3)(4)(5)(6). Due to the risk of infection and immune reactions, autologous plasma lipoproteins must be isolated and reinjected into recipient subjects, which is a laborious and time-consuming procedure.…”

“…In contrast, the same emulsion preparation can be used in an undetermined number of subjects. Furthermore, emulsions are easy to prepare and label with radioactive, fluorescent, or other markers, and bear the advantage of being standard uniform preparations (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). In contrast, native lipoproteins comprise different subclasses that vary widely among subjects, each one with distinct biological and pathophysiological properties.…”