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.