Macrophage targeting of azidothymidine: a promising strategy for AIDS therapy

AIDS Research and Human Retroviruses
R Löbenberg, J Kreuter

Abstract

Macrophages play an important role in the immunopathogenesis of AIDS. The objective of this study was to investigate the possibility of specific targeting of antivirals such as azidothymidine (AZT) to macrophages, using nanoparticles as a colloidal drug carrier. The body distribution of AZT bound to nanoparticles and as a control solution was studied in rats after intravenous and peroral administration. 14C-Labeled AZT was bound to nanoparticles in the presence of bis(2-ethylhexyl)sulfosuccinate sodium. The radioactivity was measured in different organs including those containing large numbers of macrophages. After intravenous injection, the concentrations of AZT were up to 18 times higher in organs belonging to the reticuloendothelial system (RES) when the drug was bound to nanoparticles than after injection of an aqueous AZT solution. Likewise, after oral administration the nanoparticle formulation delivered AZT more efficiently to the RES than the aqueous solution. In addition, the blood concentration was significantly higher after oral administration of nanoparticles. These results demonstrate that nanoparticles are a promising drug-targeting system for AZT to the RES organs. The increase in drug availability at the sites c...Continue Reading

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