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Erica Butti, Neuroimmunology Unit San Raffaella Scientific Institute–DIBIT Via Olgettina 58 20132 Milano Italy,
Gianvito Martino, Neuroimmunology Unit San Raffaele Scientific Institute–DIBIT Via Olgettina 58 20132 Milano Italy,
Roberto Furlan, Neuroimmunology Unit San Raffaele Scientific Institute–DIBIT Via Olgettina 58 20132 Milano Italy
Therapies targeting the central nervous system (CNS) are a crucial challenge for future medicine. In fact, degenerative and immune-mediated disorders of the CNS are a major threat to quality of life in the elderly, but diseases affecting the brain are also not infrequent in infancy and adult life. Transfer of recent progresses in the knowledge of molecular mechanisms involved in the pathogenesis of neurological disorders into novel therapies is difficult, because penetration of molecules into the brain is extremely limited by the presence of the blood–brain barrier (BBB). The BBB is characterized by tight junctions between endothelial cells which are impermeable to macromolecules and even ions, and by reduced endothelial endocytic activity that considerably decreases the number of molecules that can cross the BBB in a non-specific fashion. Most of conventional therapeutic agents effective in the CNS are supposed to cross the BBB because of their small size. However, more than 98% of small molecules cannot cross the BBB either, and only the presence of specific transport mechanisms assures that molecules essential for the brain metabolism (e.g., amino acids and glucose) reach the brain parenchyma. Thus, by employing conventional administration routes (i.e., oral, intravenous, intramuscular), which share the bloodstream as the final driving force to the brain, both rate and selectivity of the drug delivery are severely hampered, resulting in limited efficacy and potential side effects.
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