title: Systemic and local drug delivery for treating diseases of the central nervous system in rodent models.
abstract: Thorough preclinical testing of central nervous system (CNS) therapeutics includes a consideration of routes of administration and agent biodistribution in assessing therapeutic efficacy. Between the two major classifications of administration, local vs. systemic, systemic delivery approaches are often preferred due to ease of administration. However, systemic delivery may result in suboptimal drug concentration being achieved in the CNS, and lead to erroneous conclusions regarding agent efficacy. Local drug delivery methods are more invasive, but may be necessary to achieve therapeutic CNS drug levels. Here, we demonstrate proper technique for three routes of systemic drug delivery: intravenous injection, intraperitoneal injection, and oral gavage. In addition, we show a method for local delivery to the brain: convection-enhanced delivery (CED). The use of fluorescently-labeled compounds is included for in vivo imaging and verification of proper drug administration. The methods are presented using murine models, but can easily be adapted for use in rats.
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Serwer
authors.forename: Rintaro
authors.initials: R
authors.lastname: Hashizume
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ozawa
authors.forename: C David
authors.initials: CD
authors.lastname: James
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism; D018481:Convection; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods*; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000493:pharmacokinetics; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice
chemical_list: D005456:Fluorescent Dyes