Application of cyclodextrin-based metal-organic frameworks for multi-drug carriers: A combined experimental and simulation study

Combination therapy using multiple drugs has the potential for synergistic therapeutic effects and reduction in the administered dose. Furthermore, when combined with a drug delivery system, the therapeutic agents can effectively be targeted and delivered to the affected area. Therefore, a single carrier capable of encapsulating multiple drugs is of clinical significance. This study focused on cyclodextrin-based metal-organic frameworks (CD-MOFs) with high biocompatibility and hydrophobic and hydrophilic pores, because their amphiphilic pores should be suitable for encapsulating multiple drugs. First, the drug encapsulation ability of 5-fluorouracil (5FU) and ascorbic acid (ASC) into the γ-CD-MOF through experiments was compared with that of grand canonical Monte Carlo (GCMC) simulations. The drugs were suggested to encapsulate in the different pores of γ-CD-MOF depending on the hydrophilicity of the drug. In addition, the multi-drug encapsulation ability of the γ-CD-MOF was experimentally and numerically confirmed. In the simultaneous encapsulation experiments, the encapsulation amounts of 5FU and ASC were measured to be 0.0536 and 1.67 mol/mol, respectively. Also, the GCMC simulation demonstrated the simultaneous encapsulation of the two drugs, in which the loaded amounts of 5FU and ASC were calculated as 0.867 and 1.67 mol/mol, respectively. The encapsulation ability of multi-drug with hydrophilicity and hydrophobicity into the γ-CD-MOF was experimentally and numerically confirmed. The findings obtained in this study suggested that γ-CD-MOF will greatly contribute as a multi-drug carrier.