G.A. Krestov Institute of Solution Chemistry of RAS, 1 Akademicheskaya str., 153045 Ivanovo, Russian Federation.
Ufa Institute of Chemistry, Ufa Federal Research Centre of the Russian Academy of Sciences, 71, Prosp. Oktyabrya, 450054 Ufa, Russian Federation.
Mater Sci Eng C Mater Biol Appl. 2020 Jun;111:110774. doi: 10.1016/j.msec.2020.110774. Epub 2020 Feb 28.
In this work, metal-organic frameworks on the basis of γ-cyclodextrin (γCD-MOF) were proposed as carriers for methotrexate (MTX) which is widely used as chemotherapy agent and immune system suppressant. The synthesized γCD-MOF was loaded with MTX by impregnation and co-crystallization. The obtained composites were characterized using powder X-ray diffraction, N adsorption/desorption, FTIR spectroscopy, solid-state C MAS CP/TOSS NMR and scanning electron microscopy. Pharmaceutically relevant properties of MTX alone and loaded in γCD-MOF were investigated in vitro and in vivo. The faster dissolution of MTX incorporated in γCD-MOF was demonstrated in blank buffers and biorelevant media (FaSSGF, FaSSIF) simulating the gastrointestinal fluids. Inclusion complex formation of MTX with γ-CD enhances the drug dissolution rate and, at the same time, slightly decreases the drug permeability through the lipophilic membrane. The in vivo experiments showed the improved pharmacokinetic parameters of MTX loaded in γCD-MOF.
在这项工作中，提出了基于 γ-环糊精（γCD-MOF）的金属有机骨架作为甲氨蝶呤（MTX）的载体，MTX 被广泛用作化疗药物和免疫系统抑制剂。通过浸渍和共晶化将合成的 γCD-MOF 负载 MTX。使用粉末 X 射线衍射、N 吸附/解吸、FTIR 光谱、固态 C MAS CP/TOSS NMR 和扫描电子显微镜对获得的复合材料进行了表征。研究了 MTX 单独和负载在 γCD-MOF 中的药物相关性质的体外和体内情况。在空白缓冲液和生物相关介质（FaSSGF、FaSSIF）中证明了负载在 γCD-MOF 中的 MTX 具有更快的溶解速度，模拟胃肠道液体。MTX 与 γ-CD 的包合复合物形成提高了药物的溶解速率，同时，略微降低了药物通过亲脂性膜的渗透性。体内实验表明，负载在 γCD-MOF 中的 MTX 的药代动力学参数得到了改善。
