Löbenberg R, Kreuter J
Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
AIDS Res Hum Retroviruses. 1996 Dec 10;12(18):1709-15. doi: 10.1089/aid.1996.12.1709.
Macrophages play an important role in the immunopathogenesis of AIDS. The objective of this study was to investigate the possibility of specific targeting of antivirals such as azidothymidine (AZT) to macrophages, using nanoparticles as a colloidal drug carrier. The body distribution of AZT bound to nanoparticles and as a control solution was studied in rats after intravenous and peroral administration. 14C-Labeled AZT was bound to nanoparticles in the presence of bis(2-ethylhexyl)sulfosuccinate sodium. The radioactivity was measured in different organs including those containing large numbers of macrophages. After intravenous injection, the concentrations of AZT were up to 18 times higher in organs belonging to the reticuloendothelial system (RES) when the drug was bound to nanoparticles than after injection of an aqueous AZT solution. Likewise, after oral administration the nanoparticle formulation delivered AZT more efficiently to the RES than the aqueous solution. In addition, the blood concentration was significantly higher after oral administration of nanoparticles. These results demonstrate that nanoparticles are a promising drug-targeting system for AZT to the RES organs. The increase in drug availability at the sites containing abundant macrophages may allow a reduction in dosage to avoid systemic toxicity.
巨噬细胞在艾滋病的免疫发病机制中起重要作用。本研究的目的是探讨使用纳米颗粒作为胶体药物载体，将齐多夫定（AZT）等抗病毒药物特异性靶向巨噬细胞的可能性。在大鼠静脉内和口服给药后，研究了与纳米颗粒结合的AZT以及作为对照溶液的体内分布情况。在双（2-乙基己基）磺基琥珀酸钠存在下，将14C标记的AZT与纳米颗粒结合。在不同器官（包括含有大量巨噬细胞的器官）中测量放射性。静脉注射后，当药物与纳米颗粒结合时，网状内皮系统（RES）所属器官中AZT的浓度比注射AZT水溶液后高18倍。同样，口服给药后，纳米颗粒制剂比水溶液更有效地将AZT递送至RES。此外，口服纳米颗粒后血药浓度显著更高。这些结果表明，纳米颗粒是一种将AZT靶向RES器官的有前景的药物靶向系统。在含有丰富巨噬细胞的部位药物可及性的增加可能允许减少剂量以避免全身毒性。
