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  • Title: Improved body distribution of 14C-labelled AZT bound to nanoparticles in rats determined by radioluminography.
    Author: Löbenberg R, Maas J, Kreuter J.
    Journal: J Drug Target; 1998; 5(3):171-9. PubMed ID: 9606007.
    Abstract:
    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 manufactured by emulsion polymerization in the presence of AZT and an ionic emulsifier, bis(2-ethylhexyl) sulfosuccinate sodium. The AZT-control solution was equally prepared, but contained no monomer. The two preparations were administered either by i.v. injection or perorally by gavage. After determined time points the animals were sacrificed using carbon dioxide. The cadavers were shock-frozen in cellulose gel and cut into 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. After 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 showing 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 between AZT-control solution and AZT bound to nanoparticles also was visible on the images. Similar results were obtained after oral administration. Of course, with the latter route a larger portion of AZT remained in the GI-tract especially after administration of nanoparticle-bound drug. These results confirmed those obtained by a classically performed quantitative whole body distribution study using liquid scintillation. This demonstrates that radioluminography is a useful method to study the organ distribution of drugs bound to nanoparticles.
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