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. Video LinkThe video component of this article can be found at http://www.jove.com/video/1992/ Protocol Systemic Delivery MethodsAlthough systemic delivery of drugs is not the most efficient approach for achieving high drug concentrations in the CNS, systemic deliveries are convenient and well accepted by patients. Here, we will demonstrate proper procedures for three routinely used systemic administration approaches: intravenous injection, intraperitoneal injection, and oral gavage.

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