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Delivery of Anti-Hiv Nucleosides to the Central-Nervous-System
Advanced Drug Delivery Reviews. 1994 Jun-Jul;14(2-3) :199-209
AbstractThe ability of the human immunodeficiency virus (HIV) to enter and harbor in the central nervous system (CNS) results in a devastating AIDS-dementia complex. As a class, the anti-HIV nucleosides penetrate the blood-brain barrier (BBB) poorly, and drug therapy is less than optimal. A variety of drug delivery techniques has been proposed to enhance the CNS delivery of the nucleosides. These include constant rate infusions, transport inhibitors, and prodrug approaches. Evaluation of these methods in various animal models has not always differentiated vascular, extravascular and cerebrospinal fluid drug concentrations, and has led to some controversies with regard to CNS uptake of the nucleosides. The application of brain microdialysis to quantitate brain disposition will facilitate assessment of BBB transport. Due to the insidious nature of HIV, successful drug delivery systems will not only enhance brain parenchyma concentrations, but also maintain them for a controlled period of time. Combined developments in drug delivery technologies and means to quantitate CNS drug transport should lead to improved treatment modalities.
NotesEnglish Review NT634 ADVAN DRUG DELIVERY REV