title: Apolipoprotein B-100-targeted negatively charged nanoliposomes for the treatment of dyslipidemia.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Hatamipour
authors.affiliation: Cardiovascular Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Majid
authors.initials: M
authors.lastname: Ghayour-Mobarhan
authors.affiliation: Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran; Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address: jafarimr@mums.ac.ir.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D053299:Apolipoprotein B-100 / Q000037:antagonists & inhibitors* / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D050171:Dyslipidemias / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D053299:Apolipoprotein B-100; D008074:Lipoproteins; D008081:Liposomes; D010743:Phospholipids; D002784:Cholesterol
keywords: Cholesterol; Dyslipidemia; Liposome; Monoclonal antibody; Phospholipid