MACROPHAGE TARGETING OF AZIDOTHYMIDINE - A PROMISING STRATEGY FOR AIDS THERAPY

Macrophages play an important role in the immunopathogenesis of AIDS, The objective of this study was to investigate the possibility of spec ific targeting of antivirals such as azidothymidine (AZT) to macrophag es, using nanoparticles as a colloidal drug carrier, The body distribu tion of AZT bound to nanoparticles and as a control solution was studi ed in rats after intravenous and peroral administration, C-14-Labeled AZT was bound to nanoparticles in the presence of bis(2-ethylhexyl)sul fosuccinate sodium, The radioactivity was measured in different organs including those containing large numbers of macrophages. After intrav enous injection, the concentrations of AZT were up to 18 times higher in organs belonging to the reticuloendothelial system (RES) when the d rug was bound to nanoparticles than after injection of an aqueous AZT solution, Likewise, after oral administration the nanoparticle formula tion delivered AZT more efficiently to the RES than the aqueous soluti on, In addition, the blood concentration was significantly higher afte r oral administration of nanoparticles. These results demonstrate that nanoparticles are a promising drug-targeting system for AZT to the RE S organs. The increase in drug availability at the sites containing ab undant macrophages may allow a reduction in dosage to avoid systemic t oxicity.