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.
Highlights
Among the several physical characteristics of solid nanoparticles designed for drug delivery, the particle size is a prominent one [1,2]
We have shown that cholesterolrich nanoparticles termed Lipid nanoparticles (LDE) are taken-up by the lowdensity lipoprotein (LDL) receptors after injection into the bloodstream [7]
It was shown that the size of the lipid nanoparticles, at least within the 20–100 nm diameter range, was not determinant for treatment outcome of paclitaxel carried in LDE in rabbits with atherosclerosis
Summary
Among the several physical characteristics of solid nanoparticles designed for drug delivery, the particle size is a prominent one [1,2]. Regarding the nanoparticles that can actively bind to targeted cells, the affinity of the ligands with cell membrane surfaces can be largely dependent of particle size [5]. As cancer cells show upregulation of LDL receptors, LDE can be used as vehicle to direct antineoplastic drugs to those cells. It was shown in in vitro studies that LDE internalizes drugs such as carmustine, etoposide, and paclitaxel into cultured neoplastic cells [7,17,18]. In studies enrolling patients with advanced multi-drug resistant cancers, it was shown that carmustine, etoposide, and paclitaxel showed a remarkable reduction of clinical and laboratorial toxicity when associated to LDE [12,17,23]
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