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

  • Curr Vasc Pharmacol. 2022;20(1):69-76. doi: 10.2174/1570161119666210820115150.
Amir Abbas Momtazi-Borojeni  1 ,  Elham Abdollahi  2 ,  Mahmoud R Jaafari  3 ,  Maciej Banach  4 ,  Gerald F Watts  5 ,  Amirhossein Sahebkar  6
Affiliations
  • 1. Department of Medical Biotechnology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran.
  • 2. Department of Gynecology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • 3. Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  • 4.
  • 5. Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland
  • 6.
  • 7. Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
  • 8. Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
  • 9.
  • 10.
  • 11.
PMID: 34414873 DOI: 10.2174/1570161119666210820115150
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; lipoprotein.; nanoparticles; phosphoglycerol.
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