Li Xue, Guo Tao, Lachmanski Laurent, Manoli Francesco, Menendez-Miranda Mario, Manet Ilse, Guo Zhen, Wu Li, Zhang Jiwen, Gref Ruxandra
Institut des Sciences Moléculaires d'Orsay, UMR CNRS 8214, Paris-Sud University, Paris Saclay, 91400 Orsay, France; Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Center for Drug Delivery System, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Int J Pharm. 2017 Oct 15;531(2):424-432. doi: 10.1016/j.ijpharm.2017.05.056. Epub 2017 May 26.
Cyclodextrin-based metal-organic frameworks (CD-MOFs) represent an environment-friendly and biocompatible class of MOFs drawing increasing attention in drug delivery. Lansoprazole (LPZ) is a proton-pump inhibitor used to reduce the production of acid in the stomach and recently identified as an antitubercular prodrug. Herein, LPZ loaded CD-MOFs were successfully synthesized upon the assembly with γ-CD in the presence of K ions using an optimized co-crystallization method. They were characterized in terms of morphology, size and crystallinity, showing almost perfect cubic morphologies with monodispersed size distributions. The crystalline particles, loaded or not with LPZ, have mean diameters of around 6μm. The payloads reached 23.2±2.1% (wt) which corresponds to a molar ratio of 1:1 between LPZ and γ-CD. It was demonstrated that even after two years storage, the incorporated drug inside the CD-MOFs maintained its spectroscopic characteristics. Molecular modelling provided a deeper insight into the interaction between the LPZ and CD-MOFs. Raman spectra of individual particles were recorded, confirming the formation of inclusion complexes within the tridimensional CD-MOF structures. Of note, it was found that each individual particle had the same chemical composition. The LPZ-loaded particles had remarkable homogeneity in terms of both drug loading and size. These results pave the way towards the use of CD-MOFs for drug delivery purposes.
基于环糊精的金属有机框架材料（CD-MOFs）是一类环境友好且具有生物相容性的金属有机框架材料，在药物递送领域正受到越来越多的关注。兰索拉唑（LPZ）是一种质子泵抑制剂，用于减少胃酸分泌，最近被确定为一种抗结核前体药物。在此，采用优化的共结晶方法，在钾离子存在下，通过与γ-环糊精组装成功合成了负载LPZ的CD-MOFs。对其形态、尺寸和结晶度进行了表征，显示出几乎完美的立方形态，尺寸分布单分散。负载或未负载LPZ的结晶颗粒平均直径约为6μm。载药量达到23.2±2.1%（重量），这对应于LPZ与γ-环糊精之间1:1的摩尔比。结果表明，即使储存两年后，CD-MOFs中所含药物仍保持其光谱特征。分子模拟为深入了解LPZ与CD-MOFs之间的相互作用提供了依据。记录了单个颗粒的拉曼光谱，证实了在三维CD-MOF结构内形成了包合物。值得注意的是，发现每个单个颗粒具有相同的化学组成。负载LPZ的颗粒在载药量和尺寸方面均具有显著的均匀性。这些结果为将CD-MOFs用于药物递送目的铺平了道路。
