alexa Enhanced delivery of ganciclovir to the brain through the use of redox targeting.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Brewster ME, Raghavan K, Pop E, Bodor N

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Abstract Enhanced delivery of ganciclovir to the brain was demonstrated by a redox-based chemical delivery system. A ganciclovir monoester in which a 1-methyl-1,4-dihydronicotinate was covalently attached to one of the hydroxymethyl functions was prepared. The stability of the ganciclovir chemical delivery system (DHPG-CDS) was evaluated in aqueous buffers and organ homogenates. In vivo distribution studies in the rat indicated that while ganciclovir poorly penetrated into the central nervous system and was rapidly eliminated, DHPG-CDS provided for therapeutically relevant (2.7 microM) and sustained levels of the parent compound through 6 h. An analysis of the area under the concentration curve indicated that the chemical delivery system delivered five times more ganciclovir than that of the parent drug. The high levels in the brain and reduced levels in the blood gave a brain-to-blood drug concentration ratio of 2.54 for ganciclovir when delivered by the chemical delivery system, compared to a ratio of 0.063 when the parent drug was administered. These data suggest that DHPG-CDS could be a useful adjunct for the treatment of cytomegalovirus encephalitis.
This article was published in Antimicrob Agents Chemother and referenced in Journal of Bioequivalence & Bioavailability

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