Title:Negatively-charged Liposome Nanoparticles Can Prevent Dyslipidemia and Atherosclerosis Progression in the Rabbit Model
Volume: 20
Issue: 1
Author(s): Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Mahmoud R. Jaafari, Maciej Banach, Gerald F. Watts and Amirhossein Sahebkar*
Affiliation:
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical
Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Medicine, The University of Western Australia, Perth, Australia
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
Keywords:
Atherosclerosis, anionic nanoliposome, dyslipidaemia, phosphoglycerol, nanoparticles, lipoprotein.
Abstract:
Background and Aim: Negatively charged nanoliposomes have a strong attraction towards
plasma lipoprotein particles and can thereby regulate lipid metabolism. Here, the impact of
such nanoliposomes on dyslipidaemia and progression of atherosclerosis was investigated in a rabbit
model.
Methods: Two sets of negatively-charged nanoliposome formulations including [Hydrogenated
Soy Phosphatidylcholine (HSPC)/1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)] and [1,2-
Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC)/1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine
(DMPG)/Cholesterol] were evaluated. Rabbits fed a high-cholesterol diet were randomly divided
into 3 groups (n=5/group) intravenously administrated with HSPC/DSPG formulation (DSPG
group; 100 mmol/kg), DMPC/DMPG formulation (DMPG group; 100 mmol/kg), or the normal
saline (control group; 0.9% NaCl) over a 4-week period. The atherosclerotic lesions of the aortic
arch wall were studied using haematoxylin and eosin staining.
Results: Both DSPG and DMPG nanoliposome formulations showed a nano-sized range in diameter
with a negatively-charged surface and a polydispersity index of <0.1. After 4 weeks administration,
the nanoliposome formulations decreased triglycerides (-62±3% [DSPG group] and -58±2%
[DMPG group]), total cholesterol (-58±9% [DSPG group] and -37±5% [DMPG group]), and lowdensity
lipoprotein cholesterol (-64±6% [DSPG group] and -53±10% [DMPG group]) levels, and
increased high-density lipoprotein cholesterol (+67±28% [DSPG group] and +35±19% [DMPG
group]) levels compared with the controls. The nanoliposomes showed a significant decrease in the
severity of atherosclerotic lesions: mean values of the intima to media ratio in DMPG (0.96±0.1
fold) and DSPG (0.54±0.02 fold) groups were found to be significantly lower than that in the control
(1.2±0.2 fold) group (p<0.05).
Conclusion: Anionic nanoliposomes containing [HSPC/DSPG] and [DMPC/DMPG] correct dyslipidaemia
and inhibit the progression of atherosclerosis.
