title: Prodrug approaches for CNS delivery.
abstract: Central nervous system (CNS) drug delivery remains a major challenge, despite extensive efforts that have been made to develop novel strategies to overcome obstacles. Prodrugs are bioreversible derivatives of drug molecules that must undergo an enzymatic and/or chemical transformation in vivo to release the active parent drug, which subsequently exerts the desired pharmacological effect. In both drug discovery and drug development, prodrugs have become an established tool for improving physicochemical, biopharmaceutical or pharmacokinetic properties of pharmacologically active agents that overcome barriers to a drug's usefulness. This review provides insight into various prodrug strategies explored to date for CNS drug delivery, including lipophilic prodrugs, carrier- and receptor-mediated prodrug delivery systems, and gene-directed enzyme prodrug therapy.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211, Kuopio, Finland. jarkko.rautio@uku.fi
authors.forename: Jarkko
authors.initials: J
authors.lastname: Rautio
authors.forename: Krista
authors.initials: K
authors.lastname: Laine
authors.forename: Mikko
authors.initials: M
authors.lastname: Gynther
authors.forename: Jouko
authors.initials: J
authors.lastname: Savolainen
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D004364:Pharmaceutical Preparations; D011355:Prodrugs