Influence of Solvents on Drug Loading Capacity of Metal–Organic Frameworks Focusing on Solvent Dipole Moment

The application of metal-organic frameworks (MOFs) as drug delivery systems with a high drug-loading capacity and targeted delivery is advancing rapidly. This study is the first to elucidate the mechanism of drug-loading in MOFs. It focused on the crucial role of solvents in drug-loading capacity. Ibuprofen, which is widely used as a nonsteroidal antiflammatory drug, was selected as a model drug. The drug-loading capacities of zeolitic imidazolate framework-8 (ZIF-8) and Universitetet i Oslo-66-NH₂ (UiO-66-NH₂) were investigated in various solvents. For ZIF-8, an increase in the solvent dipole moment corresponded to an increase in the drug-loading capacity. Intriguingly, the converse trend was observed for UiO-66-NH₂. Therein, a decrease in the solvent dipole moment caused an increase in the drug-loading. These observations indicated that the solvent dipole moment plays a critical role in the drug-loading mechanism of the MOFs. Furthermore, Raman spectroscopy in the solvents with different polarities revealed significant variations in the molecular vibrations of ZIF-8 and UiO-66-NH₂. It was indicated that in both the MOFs, the drug-loading amount increased in the solvents when the molecular vibrations of the MOF were constrained. This study revealed that the solvent plays a crucial role in the drug-loading in MOFs, and the polarity of the solvents contributes significantly to the molecular vibration of MOFs during drug-loading, thereby affecting the drug-loading capacity.