The blood-brain barrier (BBB) limits the distribution of systemically administered therapeutics to the central nervous system (CNS), posing a significant challenge to drug development efforts to treat neurological and psychiatric diseases and disorders. A growing body of evidence demonstrates that intranasal administration of a broad spectrum of therapeutics results in significant delivery to the cerebrospinal fluid (CSF), brain and spinal cord in animals and in humans. While the exact mechanisms underlying intranasal delivery to the CNS are not understood, olfactory and trigeminal nerves, which connect the nasal cavity and the CNS, clearly play an important role in direct delivery to the CNS. In addition, pathways involving the vasculature, cerebrospinal fluid and lymphatic system have also been implicated in the transport of molecules from the nasal cavity to the CNS. Combination of these pathways into the CNS is likely followed after intranasal administration and may be heavily dependent on the specific properties of the therapeutic as well as the composition of the nasal formulation. In the last decade, research efforts have focused on improving delivery efficiency and drug targeting to the CNS with the intranasal method by using a variety of formulations strategies including solution, nanoparticle, microspheres microemulsion and nanoemulsion.
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