Albumin Nanoparticles for Brain Delivery: A Comparison of Chemical versus Thermal Methods and invivo Behavior

Human serum albumin (HSA) nanoparticles (NPs) have gained considerable attention owing to their high loading capacity of various drugs and being well tolerated. The aim of this work was the investigation of two different preparation methods to produce NPs without using organic solvents, and to obtain useful drug delivery systems to cross the blood-brain barrier. NPs were obtained by coacervation using both chemical (HSAC) and thermal cross-linking (HSAT). NPs were developed and optimised to target brain tissues after intravenous and intraperitoneal 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 behavioural test. All NPs were chemically and phisically characterized by DLS, TEM and HPLC-DAD- FLD analyses. Distribution and fate of NPs in the brain were evaluated by fluorescent microscope images. NPs were able to cross the blood-brain barrier and reach brain tissue and did not induce inflammatory response. Behavioural test demonstrated no locomotor, explorative and cognitive functions impairment induced by NPs.