Improving Brain Drug Targeting Through Exploitation of The Nose-to- Brain Route: A Physiological and Pharmacokinetic Perspective
With an ageing population and increasing prevalence of central-nervous system (CNS) disorders new approaches
are required to sustain the development and successful delivery of therapeutics into the brain and CNS. CNS
drug delivery is challenging due to the impermeable nature of the brain microvascular endothelial cells that form the
blood-brain barrier (BBB) and which prevent the entry of a wide range of therapeutics into the brain. This review examines
the role intranasal delivery may play in achieving direct brain delivery, for small molecular weight drugs, macromolecular
therapeutics and cell-based therapeutics, by exploitation of the olfactory and trigeminal nerve pathways. This approach
is thought to deliver drugs into the brain and CNS through bypassing the BBB. Details of the mechanism of transfer
of administrated therapeutics, the pathways that lead to brain deposition, with a specific focus on therapeutic pharmacokinetics,
and examples of successful CNS delivery will be explored.
Keywords: Blood-brain barrier, brain, central nervous system, nasal, neuron, olfactory, pharmacokinetics, trigeminal.
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