Body distribution of azidothymidine bound to nanoparticles after oral administration

Reticuloendothelial cells play an important role in the immunopathogenesis of AIDS. For this reason, a targeted delivery of antiviral drugs to these cells should significantly improve therapy of AIDS. The objective of the present study was to investigate the possibility of specific drug targeting of antiviral drugs to the reticuloendothelial cells by the oral route. Hexylcyanoacrylate nanoparticles were used as colloidal drug carriers for azidothymidine (AZT). C-14-labelled AZT was bound to nanoparticles using bis(2-ethylhexyl) sulfosuccinate sodium as surfactant. The radioactivity in several organs including those containing large numbers of macrophages was measured after peroral administration of the nanoparticle preparation and compared to a [C-14]AZT control solution containing the same components without the nanoparticles. In the liver the area under the curve (AUG) of [C-14]AZT was 30% higher when the drug was bound to nanoparticles than after administration of the solution. In addition, higher [C-14]AZT concentrations were observed after I hour and at later time points in blood and brain when nanoparticles were used compared to the control solution. These results indicate that nanoparticles are a promising drug targeting system for nucleoside analogues. Furthermore, the increase in drug availability at sites containing abundant macrophages, e.g. in the blood and in the brain, may allow a reduction in dosage and a decrease in systemic toxicity. (C) 1997 Elsevier Science B.V.