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Systemic and Local Drug Delivery for Treating Diseases of the Central Nervous System in Rodent Models
Authors:Laura Serwer   Rintaro Hashizume   Tomoko Ozawa   C. David James
Affiliation:Department of Neurological Surgery, University of California, San Francisco - UCSF
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.
Keywords:Neuroscience   Issue 42   mouse   in vivo optical imaging   preclinical   central nervous system   fluorescent imaging   convection-enhanced delivery   oral gavage   intravenous injection   intraperitoneal injection
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