Direct transport theory: From the nose to the brain

The delivery of drugs to CNS has been constrained due to the presence of blood-brain barrier (BBB). The intranasal route involving several pathways (viz., olfactory, trigeminal, and rostral migratory stream-based pathway) has emerged as potential route to bypass the BBB and transport drug directly to the brain. In another terms, intranasal route involves two distinct mechanistic transportation pathways, viz., extracellular and intracellular. Extracellular pathway is responsible for the transportation of drug directly to cerebrospinal fluid (CSF) by passing through paracellular space across the nasal epithelium, then through the perineuronal space to the subarachnoid space of the brain. However, intracellular pathways start with olfactory sensory cell-based endocytosis, followed by axonal transportation to their synaptic clefts in the olfactory bulb where the therapeutic moiety is exocytosed. This chapter inculcates various pathways and transport mechanisms involved in the direct transportation of drugs to the brain. The several case studies involving pharmacokinetics of nanoparticle-based delivery systems when administered intranasally have also been explained in this chapter.