Simon-Yarza T, Baati T, Neffati F, Njim L, Couvreur P, Serre C, Gref R, Najjar M Fadhel, Zakhama A, Horcajada P
Institut Lavoisier, Université de Versailles St Quentin, UMR CNRS 8180, 45 avenue des Etats-Unis, 78035 Versailles, France.
Laboratoire de Biochimie et de Toxicologie, CHU de Monastir, Tunisie.
Int J Pharm. 2016 Sep 25;511(2):1042-7. doi: 10.1016/j.ijpharm.2016.08.010. Epub 2016 Aug 8.
Metal-organic frameworks have shown interesting features for biomedical applications, such as drug delivery and imaging agents. The benchmarked mesoporous iron(III) trimesate MIL-100 MOF nanocarrier combines progressive release of high drug cargoes with absence of visible in vivo toxicity. Although in a previous study pharmacokinetics and biodistribution of MIL-100 nanoparticles were evaluated in the long term (from 24h to 1 month), the crucial times for drug targeting and delivery applications are shorter (up to 24h). Thus, this work aims to study the blood circulating profile and organ accumulation of MIL-100 nanocarrier at early times after administration. For this purpose, after intravenous administration to rats, both constitutive components of MIL-100 (trimesate and iron) were quantified by high performance liquid chromatography and a spectrophotometric method, respectively. The pharmacokinetic profile suggested that the nanoparticles act as a depot in the blood stream during the first hours before being cleared. Accumulation took mainly place in the liver and, in some extent, in the spleen. Nevertheless, histological studies demonstrated the absence of morphological alterations due to the presence of the particles in these organs. Liver function was however slightly altered as reflected by the increased plasma aspartate aminotransferase concentrations. Finally trimesate was progressively eliminated in urine.
金属有机框架在生物医学应用中展现出了有趣的特性,比如药物递送和成像剂。作为基准的介孔均苯三酸铁(III)MIL-100金属有机框架纳米载体,能将高载药量的缓释与体内无明显毒性相结合。尽管在之前的一项研究中对MIL-100纳米颗粒的药代动力学和生物分布进行了长期评估(从24小时到1个月),但药物靶向和递送应用的关键时间更短(最长24小时)。因此,这项工作旨在研究给药后早期MIL-100纳米载体的血液循环情况和器官蓄积。为此,在对大鼠进行静脉给药后,分别通过高效液相色谱法和分光光度法对MIL-100的两种组成成分(均苯三酸和铁)进行了定量分析。药代动力学曲线表明,纳米颗粒在被清除之前的最初几个小时内在血流中起到了储存库的作用。蓄积主要发生在肝脏,在一定程度上也发生在脾脏。然而,组织学研究表明,这些器官中存在颗粒并未导致形态学改变。不过,血浆天冬氨酸转氨酶浓度升高反映出肝功能略有改变。最后,均苯三酸在尿液中被逐渐清除。