A combined experimental and computational study of novel nanocage-based metal-organic frameworks for drug delivery

• Published in: Dalton transactions : an international journal of inorganic chemistry 2015-01, Vol.44 (44), p.19370-19382
• Main Authors: Liu, Jian-Qiang, Li, Xue-Feng, Gu, Chu-Ying, da Silva, Júlio C S, Barros, Amanda L, Alves, Jr, Severino, Li, Bao-Hong, Ren, Fei, Batten, Stuart R, Soares, Thereza A
• Format: Article
• Language: English
• Subjects: Adsorption; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - chemistry; Cages; Computer Simulation; Crystallography, X-Ray; Drug Delivery Systems; Drugs; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Gas Chromatography-Mass Spectrometry; Metal-organic frameworks; Models, Molecular; Monte Carlo Method; Monte Carlo methods; Nanoparticles - chemistry; Nanostructure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - pharmacology; Porosity; Topology
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c5dt02171e

Three new metal organic frameworks (MOFs) with chemical formulae [(CH3)2NH2] [Sm3(L1)2(HCOO)2(DMF)2(H2O)]·2DMF·18H2O (1), [Cu2(L2)(H2O)2]·2.22DMA (2) and [Zn2(L1)(DMA)]·1.75DMA were synthesized and structurally characterized. 1 and 2 show a classical NbO-like topology and have two types of interconnected cages. 3 exhibits an uncommon zzz topology and has two types of interconnected cages. These MOFs can adsorb large amounts of the drug 5-fluorouracil (5-FU) and release it in a progressive way. 5-FU was incorporated into desolvated 1, 2 and 3 with loadings of 0.40, 0.42, and 0.45 g g(-1), respectively. The drug release rates were 72%, 96% and 79% of the drug after 96 hours in 1, 120 hours in 2 and 96 hours in 3, respectively. Grand Canonical Monte Carlo (GCMC) simulations were performed to investigate the molecular interactions during 5-FU adsorption to the three novel materials. The GCMC simulations reproduced the experimental trend with respect to the drug loading capacity of each material. They also provided a structural description of drug packing within the frameworks, helping to explain the load capacity and controlled release characteristics of the materials. 5-FU binding preferences to 1, 2 and 3 reflect the diversity in pore types, chemistry and sizes. The calculated drug load is more related to the molecular properties of accessible volume Vacc than to the pore size.