Background: Anionic nanoliposomes can interact with serum lipoproteins and regulate lipid metabolism through several mechanisms. This study aimed to evaluate the lipid-modifying effects of anionic immunoliposomes targeted against apoB, an important component of atherogenic lipoproteins.
Methods: Two sets of nanoliposomes (20mM) were prepared with low (including soy phosphatidylcholine [SPC] and egg phosphatidylglycerol [EPG]) and high (including hydrogenated soy phosphatidylcholine [HSPC] and distearoyl phosphatidylglycerol [DSPG]) phase transition temperature values without cholesterol. In each set, the anionic phospholipid (EPG or DSPG) constituted 75% of total phospholipid content. Immunoliposomes were prepared by conjugating a monoclonal antibody against apoB-100 to the liposomal surface using a post-insertion technique. Fluorescently-labeled immunoliposomes were assessed for their uptake by J774.A1 macrophages. Lipid-modifying effects of immunoliposomes were tested at different doses (50, 100 or 200μmole/g weight) using a tyloxapol-induced hyperlipidemic mouse model. Blood sampling was performed 1h after the injection of each immunoliposomal formulation.
Results: ApoB-targeted HSPC/DSPG and SPC/EPG nanoliposomes were both taken up by cultured macrophages but the uptake rate was higher with the former formulation. Both immunoliposomal formulations significantly reduced serum LDL-cholesterol concentrations of hyperlipidemic animals at all tested doses (p<0.001) and this effect lasted for at least 48h. Significant reductions of serum levels of apoB, non-HDL-C, total cholesterol and triglycerides, and elevations of HDL-C levels were also observed.
Conclusion: Intravenous injection of a single dose of apoB-targeted anionic nanoliposomes improves serum lipid profile parameters. These findings might have implications for the treatment of patients with severe dyslipidemias or statin intolerance.
Keywords: Cholesterol; Dyslipidemia; Liposome; Monoclonal antibody; Phospholipid.
Copyright © 2015 Elsevier B.V. All rights reserved.