Human serum albumin nanoparticles (NPs) have gained considerable attention owing to their high loading capacity for various drugs and the fact that they are well tolerated. The aim of this work was to investigate two different methods to produce NPs without the use of organic solvents and to obtain useful drug-delivery systems to cross the blood-brain barrier. NPs were obtained by coacervation, using both chemical and thermal cross-linking processes. They were developed and optimized to target brain tissues after parenteral administration in healthy rats. Furthermore, their distribution, cellular uptake, and fate were investigated in vivo after intracerebral injection in healthy rats. The toxicity of the developed carriers was estimated by behavioral tests. All NPs were chemically and physically characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography coupled with diode array and fluorimetric detectors. Their distribution and fate in the brain were evaluated by fluorescence microscopy. NPs were observed to be located in different brain tissues depending on the mode of injection, and did not induce an inflammatory response. Behavioral tests demonstrated no locomotor, explorative, or cognitive function impairment induced by the NPs.
Keywords: cross-linking; drug delivery; green chemistry; in vivo studies; nanoparticles.
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