Apolipoprotein B-100-targeted negatively charged nanoliposomes for the treatment of dyslipidemia

Colloids Surf B Biointerfaces. 2015 May 1:129:71-8. doi: 10.1016/j.colsurfb.2015.03.012. Epub 2015 Mar 7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Apolipoprotein B-100 / antagonists & inhibitors*
  • Apolipoprotein B-100 / immunology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cholesterol / chemistry
  • Cholesterol / metabolism
  • Drug Delivery Systems*
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / metabolism
  • Dyslipidemias / pathology
  • Lipoproteins / chemistry
  • Lipoproteins / metabolism
  • Liposomes*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Nanoparticles / chemistry*
  • Phospholipids / chemistry
  • Phospholipids / metabolism

Substances

  • Antibodies, Monoclonal
  • Apolipoprotein B-100
  • Lipoproteins
  • Liposomes
  • Phospholipids
  • Cholesterol