Löbenberg R, Maas J, Kreuter J
Department of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt, Germany.
J Drug Target. 1998;5(3):171-9. doi: 10.3109/10611869808995872.
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.
本研究的目的是可视化与纳米颗粒结合的放射性标记齐多夫定（AZT）和对照溶液在体内分布的差异。聚己基氰基丙烯酸酯纳米颗粒是在AZT和离子乳化剂双（2-乙基己基）磺基琥珀酸钠存在下通过乳液聚合制备的。AZT对照溶液的制备方法相同，但不含单体。两种制剂通过静脉注射或经口灌胃给药。在确定的时间点后，使用二氧化碳处死动物。将尸体在纤维素凝胶中速冻，然后用冷冻切片机切成薄片。将组织横截面固定在胶带上，然后进行冷冻干燥。通过放射自显影对不同器官和组织中的放射性AZT进行定量，并在计算机上生成图像。静脉注射AZT纳米颗粒后，在属于网状内皮系统的器官中发现了大量的AZT标记。在这些器官中，放射性分布不均匀，表明与颗粒相关的放射性的摄取取决于器官中细胞的类型，并且与巨噬细胞的摄取一致。在胃肠道和肝脏中发现了最高的放射性。在图像上也可以看到AZT对照溶液和与纳米颗粒结合的AZT在消除途径上的差异。口服给药后获得了类似的结果。当然，通过后一种途径，尤其是在给予纳米颗粒结合药物后，更大比例的AZT保留在胃肠道中。这些结果证实了通过经典的使用液体闪烁的定量全身分布研究所获得的结果。这表明放射自显影是研究与纳米颗粒结合的药物在器官中分布的一种有用方法。
