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Negatively-Charged Liposome Nanoparticles Can Prevent Dyslipidemia and Atherosclerosis Progression in the Rabbit Model

Author(s):

Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Mahmoud R. Jaafari, Maciej Banach, Gerald F. Watts and Amirhossein Sahebkar*   Pages 1 - 8 ( 8 )

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.

Keywords:

Atherosclerosis, anionic nanoliposome, dyslipidaemia, phosphoglycerol, nanoparticles, lipoprotein.

Affiliation:

Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad



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