Löbenberg R, Araujo L, von Briesen H, Rodgers E, Kreuter J
Institute of Pharmaceutical Technology, Johann Wolfgang Goethe-University, Frankfurt Main, Germany.
J Control Release. 1998 Jan 2;50(1-3):21-30. doi: 10.1016/s0168-3659(97)00105-3.
Cells of the reticuloendothelial system (RES e.g. macrophages) play an important role in the immunopathogenesis of AIDS. The objective of the present study was to investigate the possibility of specifically targeting antiviral drugs such as azidothymidine (AZT) to macrophages using nanoparticles as colloidal drug carriers. In a first series of experiments the body distribution of 14C-labelled AZT bound to nanoparticles and a similarly prepared control solution with unbound AZT were studied in rats after intravenous injection. In a second series of experiments polysorbate 80-coated nanoparticles and a solution of AZT in saline were tested. 14C-labelled AZT was bound to nanoparticles using the surfactant bis(2-ethylhexyl) sulphosuccinate sodium (DOSS). The radioactivity in several organs, including those containing large numbers of macrophages, was measured after intravenous injection of the AZT-nanoparticles and the AZT-control solutions. AZT concentrations were up to 18 times higher in organs belonging to the RES if the drug was bound to nanoparticles compared with unbound AZT. These results demonstrate that nanoparticles are a potential drug targeting system for anti-AIDS drugs. The increase in drug concentration at the sites containing abundant macrophages may allow a reduction in dosage to reduce systemic toxicity.
网状内皮系统（RES，如巨噬细胞）的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。在第一系列实验中，研究了静脉注射后，与纳米颗粒结合的14C标记的AZT以及同样制备的未结合AZT的对照溶液在大鼠体内的分布情况。在第二系列实验中，测试了聚山梨酯80包被的纳米颗粒和AZT的生理盐水溶液。使用表面活性剂双（2-乙基己基）磺基琥珀酸钠（DOSS）将14C标记的AZT与纳米颗粒结合。静脉注射AZT纳米颗粒和AZT对照溶液后，测量了包括含有大量巨噬细胞的器官在内的多个器官中的放射性。与未结合的AZT相比，如果药物与纳米颗粒结合，RES所属器官中的AZT浓度高出多达18倍。这些结果表明，纳米颗粒是抗艾滋病药物潜在的药物靶向系统。富含巨噬细胞部位的药物浓度增加可能允许减少剂量以降低全身毒性。
