The central nervous system, one of the most delicate microenvironments of the body, is protected by the blood-brain barrier (BBB) regulating its homeostasis. BBB is a highly complex structure that tightly regulates the movement of ions of a limited number of small molecules and of an even more restricted number of macromolecules from the blood to the brain, protecting it from injuries and diseases. However, the BBB also significantly precludes the delivery of drugs to the brain, thus, preventing the therapy of a number of neurological disorders. As a consequence, several strategies are currently being sought after to enhance the delivery of drugs across the BBB. Within this review, the recently born strategy of brain drug delivery based on the use of nanoparticles, multifunctional drug delivery systems with size in the order of one-billionth of meters, is described. The review also includes a brief description of the structural and physiological features of the barrier and of the most utilized nanoparticles for medical use. Finally, the potential neurotoxicity of nanoparticles is discussed, and future technological approaches are described. The strong efforts to allow the translation from preclinical to concrete clinical applications are worth the economic investments. 1. Introduction At the beginning of the third millennium, due to prolonged ageing, neurological disorders are growing, with a consequent high social impact due to their prevalence and/or high morbidity and mortality. For the purpose of calculation of estimates of the global burden of disease, the neurological disorders are included in two categories: neurological disorders within the neuropsychiatric category and neurological disorders from other categories. Neurological disorders within the neuropsychiatric category include epilepsy, Alzheimer and other dementias, Parkinson’s disease, multiple sclerosis, and migraine. Neurological disorders from other categories include diseases and injuries which have neurological sequels such as cerebrovascular disease, neuroinfections, and neurological injuries. Neurological disorders are an important cause of mortality and constitute 12% of total deaths globally. Among the neurological disorders, Alzheimer and other dementias are estimated to constitute 2.84% of the total deaths, while cerebrovascular disease constitute about 8% of the total deaths in high income countries in 2005 [1]. Presently, there are no effective therapies for many of them. Scientific and technological researches, from molecular to behavioral levels, have been carried out in
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