Lipid core nanoparticles resembling low-density lipoprotein and regression of atherosclerotic lesions: effects of particle size

Abstract

Particles are usually polydispersed and size is an important feature for lipid-based drug delivery systems in order to optimize cell-particle interactions as to pharmacologic action and toxicity. Lipid nanoparticles (LDE) with composition similar to that of low-density lipoprotein carrying paclitaxel were shown to markedly reduce atherosclerosis lesions induced in rabbits by cholesterol feeding. The aim of this study was to test whether two LDE fractions, one with small (20–60 nm) and the other with large (60–100 nm) particles, had different actions on the atherosclerotic lesions. The two LDE-paclitaxel fractions, prepared by microfluidization, were separated by density gradient ultracentrifugation and injected (4 mg/body weight, intravenously once a week) into two groups of rabbits previously fed cholesterol for 4 weeks. A group of cholesterol-fed animals injected with saline solution was used as control to assess lesion reduction with treatment. After the treatment period, the animals were euthanized for analysis. After treatment, both the small and large nanoparticle preparations of LDE-paclitaxel had equally strong anti-atherosclerosis action. Both reduced lesion extension in the aorta by roughly 50%, decreased the intima width by 75% and the macrophage presence in the intima by 50%. The two preparations also showed similar toxicity profile. In conclusion, within the 20–100 nm range, size is apparently not an important feature regarding the LDE nanoparticle system and perhaps other solid lipid-based systems.

Biodistribution of Nanostructured Lipid Carriers in Mice Atherosclerotic Model

“…As underlined in the introduction, the potentialities of lipid core nanoparticles such as nanostructured lipid carriers to target atherosclerotic lesions have remained largely unexplored, despite few promising results [24,25,26,27,28]. However, NLC display suitable features in terms of particle size, composition, in vivo tolerance, and potential translation to the clinic (easily up-scaled production at a very reasonable cost) for nanomedicine application in the cardiovascular field.…”

“…Lipid nanoparticles prepared by nanoprecipitation/solvent diffusion method and loaded with lovastatin were shown to accumulate in macrophages and foam cells present in atherosclerotic plaques [24]. Maranhão’s group developed paclitaxel-oleate [25] and carmustine [26] loaded lipid nanoparticles produced by a microfluidization process, and showed that their intravenous administration could reduce atherosclerosis lesions in rabbits. Slightly different nanoparticles, based on a perfluorocarbon oily core, were developed in Wickline’s group for MRI atherosclerosis imaging [27] but also for therapeutic purposes [28].…”

The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy

“…In a similar study, cholesteryl-core based LMPs loaded with paclitaxel, were injected into rabbits fed a high cholesterol diet. These LMPs showed significant atheroprotection, demonstrated by a reduction in intima, lesion extension and number of macrophages in the intima [ 246 ]. Carmustine has also been loaded into cholesteryl-core LMPs and reduced the lesion size by 90% and inhibited the accumulation of macrophages, T cells and vascular SMCs at the intima in a rabbit model [ 247 ].…”

Nanostructured lipid carriers accumulate in atherosclerotic plaques of ApoE−/− mice

“…Macrophage phagocytic activity and lipoprotein metabolism are potentially implicated biological pathways to investigate. 41 NLC present strong structural similarity with chylomicrons in terms of lipid composition, and with VLDL in terms of particle size. Since Q4 now, other lipoprotein classes, LDL and HDL, have attracted attention for the design of imaging and drug delivery Figure 6.…”

“…Solid lipid nanoparticles loaded with iron oxide particles and PG12 prostacyclin, and stabilized with nucleolipids, were demonstrated to reduce in vitro platelet aggregation. 50 Lipid nanoparticles prepared by microfluidization and loaded with paclitaxel-oleate 41 or carmustine 51 were shown to reduce atherosclerosis lesions in rabbits. Wickline's group has also explored the potential of slightly different nanoparticles, based on a perfluorocarbon oily core, for MR atherosclerosis imaging 52 but also for therapeutic purposes.…”