Drug Delivery to the Central Nervous System: General Principles and Relevance to Therapy for Infections of the Central Nervous System

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Abstract
Drug delivery to the central nervous system (CNS) is of vital concern to the therapy for primary CNS disorders and the development of drug neurotoxicity. The factors influencing drug entry into the CSF include the status of the blood-brain barrier (BBB) and lipid solubility, molecular weight, pKa , protein binding, and removal of the drug from the CSF by an exit pump in the choroid plexus. The most important of these factors is the status of the complex BBB systems. The morphologic equivalent of the BBB and its specialized functions (e.g., transport of d-glucose, amino acids, and ions) are discussed in depth. Methods developed for increasing drug delivery to the CNS by circumvention and/or manipulation of the BBB have included direct injection into the CSF, administration of prodrugs or chemical delivery systems, or reversible “opening” of the BBB by hyperosmotic agents, pentylenetetrazole, etoposide, DMSO, or other agents. The relevance of these general principles to selected examples of CNS infections (i.e., gram-negative aerobic bacillary meningitis and subacute encephalopathy associated with AIDS) is emphasized.

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