Introduction

The earliest forms of therapeutic drug delivery to the central nervous system (CNS) were systemically based intravenous and oral preparations. Despite attempts to increase target concentrations with intraarterial delivery or osmotic opening of the blood-brain barrier (BBB), systemic delivery remains hindered by systemic toxicity and the need for extensive drug modification for effective (80) BBB penetration. These limitations have provided the impetus for developing strategies of localized treatment for CNS disorders, to circumvent the BBB and increase local drug concentration without systemic toxicity.

A variety of methodologies for local delivery have been developed including direct injection, polymer technology, and convection-enhanced delivery (CED). Although many of these delivery methods are in the early phases of development, they have demonstrated their superiority to systemic methods in experimental models and clinical trials (8,28). By avoiding the systemic circulation, local delivery of therapeutic agents into the CNS allows compounds to reach targeted sites more consistently without undesired tissue binding, protein binding, and enzymatic modification, to promote a more consistent drug uptake (19). The advantage of local delivery for treating CNS disorders is, therefore, the ability to achieve a sufficient concentration of drug at the site of the lesion or defined neuroanatomic region for sufficient duration to produce a therapeutic response (35).

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