A combined experimental and computational study of novel nanocage-based metal-organic frameworks for drug delivery.
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.
School of Pharmacy, Guangdong Medical University, Dongguan, 523808, P. R. China. jianqiangliu8@gdmc.edu.cn.
Jian-Qiang
JQ
Liu
Xue-Feng
XF
Li
Chu-Ying
CY
Gu
Júlio C S
JC
da Silva
Amanda L
AL
Barros
Severino
S
Alves
Bao-Hong
BH
Li
Fei
F
Ren
Stuart R
SR
Batten
Thereza A
TA
Soares
D000327:Adsorption; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D016503:Drug Delivery Systems; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D008958:Models, Molecular; D009010:Monte Carlo Method; D053758:Nanoparticles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D009942:Organometallic Compounds; D005472:Fluorouracil