title: Improving brain drug targeting through exploitation of the nose-to-brain route: a physiological and pharmacokinetic perspective.
abstract: 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.
authors.forename: R K S
authors.initials: RK
authors.lastname: Badhan
authors.forename: M
authors.initials: M
authors.lastname: Kaur
authors.forename: S
authors.initials: S
authors.lastname: Lungare
authors.affiliation: Aston University, Medicines Research Unit, Life and Health Sciences, Birmingham, B4 7ET, UK. r.k.s.badhan@aston.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Obuobi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016503:Drug Delivery Systems / Q000639:trends; D006801:Humans; D008970:Molecular Weight; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009832:Olfactory Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014276:Trigeminal Nerve / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
chemical_list: D002491:Central Nervous System Agents