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

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 [1,2Dimyristoyl-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 low density 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.

Automated summary

This study investigated the impact of negatively charged nanoliposomes on dyslipidaemia and progression of atherosclerosis in a rabbit model. The results showed that nanoliposome formulations improved dyslipidaemia and reduced the severity of atherosclerotic lesions.