BODY DISTRIBUTION OF AZIDOTHYMIDINE BOUND TO HEXYL-CYANOACRYLATE NANOPARTICLES AFTER IV INJECTION TO RATS

Cells of the reticuloendothelial system (RES e.g. macrophages) play an important role in the immunopathogenesis of AIDS. The objective of th e present study was to investigate the possibility of specifically tar geting antiviral drugs such as azidothymidine (AZT) to macrophages usi ng nanoparticles as colloidal drug carriers. In a first series of expe riments the body distribution of C-14-labelled AZT bound to nanopartic les and a similarly prepared control solution with unbound AZT were st udied in rats after intravenous injection. In a second series of exper iments polysorbate 80-coated nanoparticles and a solution of AZT in sa line were tested. C-14-labelled AZT was bound to nanoparticles using t he surfactant bis(2-ethylhexyl) sulphosuccinate sodium (DOSS). The rad ioactivity in several organs, including those containing large numbers of macrophages, was measured after intravenous injection of the AZT-n anoparticles and the AZT-control solutions. AZT concentrations were up to 18 times higher in organs belonging to the RES if the drug was bou nd to nanoparticles compared with unbound AZT. These results demonstra te that nanoparticles are a potential drug targeting system for anti-A IDS drugs. The increase in drug concentration at the sites containing abundant macrophages may allow a reduction in dosage to reduce systemi c toxicity. (C) 1998 Elsevier Science B.V.