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

Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Mahmoud R Jaafari, Maciej Banach, Gerald F Watts, Amirhossein Sahebkar

Current vascular pharmacology 2022

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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. 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. 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). Anionic nanoliposomes containing [HSPC/DSPG] and [DMPC/DMPG] correct dyslipidaemia and inhibit the progression of atherosclerosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.

Citation

Amir Abbas Momtazi-Borojeni, Elham Abdollahi, Mahmoud R Jaafari, Maciej Banach, Gerald F Watts, Amirhossein Sahebkar. Negatively-charged Liposome Nanoparticles Can Prevent Dyslipidemia and Atherosclerosis Progression in the Rabbit Model. Current vascular pharmacology. 2022;20(1):69-76