Delivery of Anti-Viral Nucleoside Analogues to the Central Nervous System
Delivery of anti-viral agents into the central nervous system (CNS) is clinically important. Direct brain infection by viral pathogens including herpes (HSV-I and II, VZV, and CMV) and AIDS virus (HIV-I and II) causes a progressive deterioration in mental function, and even death. Nucleoside analogues are a major source of clinically used anti-viral agents, although their delivery to the brain is severely limited by the presence of the blood-brain barrier and blood-cerebrospinal fluid barrier. Therefore, improvement of the delivery of these nucleoside analogues to the CNS has been investigated under various mechanisms, including metabolizing enzymes, endogenous cellular transport systems, conjugates, chemical delivery systems, and prodrugs. In this review, we will summarize the following topics: 1) Roles of hydrophobicity, protein binding, and the probenecid-sensitive transport system, in delivery of nucleoside analogues with anti-herpes or anti-HIV activity, to the CNS. 2) Role of brain tissue-localized purine metabolizing enzymes in the delivery of dideoxynucleosides with anti-HIV activity to the brain. 3) Chemical delivery systems for zidovudine (AZT) based on redox trapping within the brain.
Keywords: Anti-Viral Nucleoside Analogues, Herpes, Hsv-1, II vzv, Cmv, Aids virus, Hiv-1, Blood-brain barrier, Blood-cerebrospinal fluid barrier
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