IMPROVED BODY DISTRIBUTION OF C-14-LABELED AZT BOUND TO NANOPARTICLESIN RATS DETERMINED BY RADIOLUMINOGRAPHY

The objective of the present study is to visualize differences in the body distribution between radiolabelled AZT bound to nanoparticles and a control solution. Polyhexylcyanoacrylate nanoparticles were manufac tured by emulsion polymerization in the presence of AZT and an ionic e mulsifier, bis(2-ethylhexyl) sulfosuccinate sodium. The AZT-control so lution was equally prepared, but contained no monomer. The two prepara tions were administered either by i.v. injection or perorally by gavag e. After determined time points the animals were sacrificed using carb on dioxide. The cadavers were shock-frozen in cellulose gel and cut in to slices using a cryomicrotome. The tissue cross sections were fixed on an adhesive tape and then were freeze dried. The quantification of the radioactive AZT in the different organs and tissues was performed by radioluminography, and the images were generated on a computer. Aft er i.v. injection of AZT-nanoparticles, a high amount of the AZT label was found in the organs belonging to the reticuloendothelial system. In these organs the radioactivity was inhomogeneously distributed show ing that the uptake of the particle-associated radioactivity depended on the type of the cells located in the organs and was consistent with uptake by macrophages. The highest radioactivities were found in the GI-tract and in the liver. A difference in the elimination pathway bet ween AZT-control solution and AZT bound to nanoparticles also was visi ble on the images. Similar results were obtained after oral administra tion. Of course, with the latter route a larger portion of AZT remaine d in the GI-tract especially after administration of nanoparticle-boun d drug. These results confirmed those obtained by a classically perfor med quantitative whole body distribution study using liquid scintillat ion. This demonstrates that radioluminography is a useful method to st udy the organ distribution of drugs bound to nanoparticles.