Protective effects of anionic nanoliposomes on hyperlipidemia and atherosclerosis progression in a rabbit model

Abstract Background and purpose Anionic nanoliposomes can regulate lipid metabolism by interacting with plasma lipoproteins. Here, we aimed to investigate the protective effects of anionic nanoliposomes against hyperlipidemia and atherosclerosis in the rabbit fed a high-fat diet (HFD) recapitulating human hyperlipidemia and atherosclerosis. Methods To prepare anionic nanoliposome formulations [containing hydrogenated soy phosphatidylcholine (HSPC) and 1,2-distearoyl-sn-glycero-3- phosphoglycerol (DSPG)] and [containing 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC) and 1,2-Dimyristoyl-sn-glycero-3-phosphorylcholine (DMPG)], lipid film hydration method followed by extrusion. Physical properties of the prepared liposome formulations, including particle size (diameter, nm), polydispersity index (PDI), and surface charge, were determined using dynamic light scattering (DLS) technique. New Zealand white male rabbits (4–6 months old, weight 2±0.15 kg) were fed on a regimen chow diet containing 15% fat and 0.5% cholesterol for 8 weeks. To evaluate the protective effects of anionic nanoliposomes, treatment was primed at week 4 on animals equally divided into three groups, including rabbits receiving HSPC/DSPG formulation (DSPG group) and DMPG/DMPC formulation (DMPG group) at the dose of 100 mM/kg via intravenous administration for 4 weeks with a weekly interval, as well as control group receiving saline buffer at a same administration route. Results Anionic nanoliposomal formulations were found to significantly regulate plasma levels of lipid parameters in the rabbit model of atherosclerosis by reducing TC (by 58±9%; 95% CI: 46–70% [HSPC/DSPG] and 37 5%; 95% I: 31–44% [DMPG/DMPC]), LDL-C (by 64 6%: 95% CI: 56–72% [HSPC/DSPG] and 53±10%; 95% CI: 37–67% [DMPC/DMPG], TG (by 62±3%; 95% CI: 58–67% [HSPC/DSPG] and 58±2%; 95% CI: 55–61% [DMPC/DMPG], and elevating HDL-C (by 67±28%; 95% CI: 32–102% [HSPC/DSPG] and 35±19%; 95% CI: 11–60% [DMPC/DMPG]), when compared to the control group at the end of study. Lesion severity in treated rabbits was found to be significantly (p<0.05) lower compared to control rabbits, for which medians (interquartile range) of plaque grades in DSPG, DMPG and control groups were 1 [1–2.5], 2 [1.5–2.5], and 4 [3–4], respectively. Of note, the mean±SD of plaque size in DSPG (54±24 μm; 95% CI: 24–83 μm) and DMPG (92±24 μm; 95% CI: 62–121 μm) groups were shown to be significantly (p<0.05) smaller (−63±17% and 36±16%, respectively) than those in control group (144±28 μm, 95% CI: 109–179 μm). The mean±SD of IMT in DSPG (0.54±0.02 fold; 95% CI: 0.3–0.8 fold) and DMPG (0.96±0.1 fold; 95% CI: 0.8–1.1 fold) groups were shown to be significantly (p<0.05) smaller (−55±17% and −20±4%, respectively) than those in control group (1.2±0.2 fold; 95% CI: 0.9–1.4 fold) (Figure). Conclusion Aninonic nanoliposomes containing [HSPC/DSPG] and [DMPC/DMPG] could significantly protect against hyperlipidemia and atherosclerosis plaque progression in rabbit model. Funding Acknowledgement Type of funding source: None