Abstract
This study describes the preparation, characterization, in vitro uptake and in vivo biodistribution in mice of solid lipid nanoparticles and nanostructured lipid carriers. The effect of nanoparticle lipid matrix, presence of fluorescent and functionalization by polysorbate 80 on dimensional distribution and morphology have been studied by sedimentation field flow fractionation, photon correlation spectroscopy and cryogenic transmission electron microscopy. The complementary use of different techniques demonstrated that lipid matrix composition, presence of fluorescent dye and polysorbate 80 functionalization have little effect on nanoparticle morphology and size distribution. Uptake of fluorescent nanoparticles was determined in vitro by human brain endothelial cells, showing that nanoparticles treated by polysorbate 80 displayed lower uptake values with respect to the corresponding control nanoparticles. Biodistribution of solid lipid nanoparticles treated by polysorbate 80 was evaluated by fluorescent luminescent imaging after intraperitoneal administration in mice. The in vivo images indicate that nanoparticles were able to reach the brain, even if they prevalently accumulated in liver and spleen.
Highlights
In recent years lipid nanoparticles have been proposed in a number of pharmaceutical research studies as drug delivery formulations, due to their versatility and advantages [1,2]
Production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) was performed by a two-step protocol based on the emulsification of the molten lipid phase in an aqueous phase containing poloxamer 188 under high speed stirring at 15000 rpm, followed by treatment with probe ultrasound
The reported results has evidenced that the complementary use of different techniques enables to fully characterize size, size distribution and morphology of nanoparticles, overcoming the specific drawbacks associated to any characterization technique
Summary
In recent years lipid nanoparticles have been proposed in a number of pharmaceutical research studies as drug delivery formulations, due to their versatility and advantages [1,2]. The lipid based excipients constituting their solid matrix: (i) allow the solubilization of lipophilic molecules in a biocompatible and biodegradable environment with well-established safety profiles, (ii) improve the stability of labile molecules and (iii) ensure controlled release profile [2,3]. Lipid nanoparticles can be administered by different routes and targeted to specific organs, such as the brain. At this regard, many investigations have been published, describing the use of lipid nanoparticles as delivery system able to overcome the blood brain barrier (BBB) [5,6,7]. Depending on the nature of the lipids constituting nanoparticle matrix, solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) can be distinguished
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