(512a) Experimental and Monte Carlo Simulation Study on Elucidation of Drug-Loading Mechanism into Uio-66 Series Focusing on Solvent and Functional Group of Linkers

Metal–organic frameworks (MOFs) are expected to be used as carriers for drug delivery systems. Encapsulation drugs into MOF pores is necessary to utilize MOFs as a drug carrier. Drugs are generally loaded into MOFs by stirring MOF particles and drugs in liquid-phase solvent. It is essential to identify the mechanism of drug encapsulation in MOFs. So far, most of the studies on the MOFs as a drug carrier are limited to case studies about a certain drug-loading into a certain MOF. Furthermore, the effect of solvent on drugs loading capacity has not been investigated. The details of solvent-induced intermolecular MOF-drug-solvent interactions are still unknown. Therefore, this study focused on solvent dipole and functional group of linkers with MOFs to investigate the effect of MOF-drug-solvent interactions on drug-loading capacity of MOFs.

In this study, we selected UiO-66-X (X = NH₂, H, Br, COOH, NO₂) based on zirconium ion and terephthalic acid as MOFs and ibuprofen (IBU) as model drug. Hexane, methanol, ethanol, water, acetone, and N,N-dimethylformamide (DMF) were used to evaluate the drug loading capacity of MOFs under different dipole conditions. Drugs and the synthesized MOF particles were stirred in different solvents. The drug loading capacity was comprehensively evaluated based on the UV-vis absorbance, thermogravimetric analysis, SEM observation, and XRD measurement. The IBU loading capacity under various solvents showed that as the solvent dipole moment increased from hexane to DMF, the amount of drug loaded into UiO-66 series gradually decreased. The decrease was related to the induced polarization of functional group with UiO-66 linkers. Focusing on the electron-donating or electron-withdrawing functional groups with ligands, UiO-66-NH₂ with the electron-donating properties of linkers had large drug amount into pores. Meanwhile, each drug amount encapsulated in UiO-66 series gradually decreased in the order of increasing electron-withdrawing effect of linker in the UiO-66 series. Therefore, solvents and functional groups of linkers significantly affected on IBU-loading capacity and stability of IBU in MOF pores.

To investigate the MOF-drug-solvent interactions in detail, drug encapsulation in MOFs was simulated using both grand canonical Monte Calro (GCMC) and canonical Monte Calro (CMC) methods. The potential energies among MOF, drug, and solvent were examined, because these were related to the MOF-drug-solvent interactions. The simulated results showed that the effect of solvent-MOF interaction and drug-solvent interaction was strongly related to experimental drug-loading capacity. Specifically, the experimental conditions, under which drug encapsulation was possible, showed lower effect of solvent in UiO-66 pores and higher drug-solvent interaction compared to those under which drug inclusion was not possible. Thus, we elucidated the relationship between drug-loading capacity in MOFs and MOF-drug-solvent interaction.