Metal–Organic Frameworks (MOFs) are porous coordination complexes formed through the self-assembly of metal ions and organic ligands. Due to their high porosity, tunable pore properties, and structural versatility, MOFs hold great promise for practical applications. One of the fields in which MOFs are expected to be utilized is the pharmaceuticals, particularly in drug delivery systems (DDS). MOFs are considered suitable carriers for DDS because of their high drug-loading capacity, adjustable pore sizes, large surface area, and the potential for structural modification. However, a major challenge in the practical application of MOF-based drug carriers is biocompatibility.
Among MOFs, cyclodextrin-based MOFs (CD-MOF), which are highly biocompatible, have recently gained significant attention as potential drug carriers. CD possesses a cyclic structure with a hydrophobic interior and a hydrophilic exterior, which imparts CD-MOFs with both hydrophobic and hydrophilic pores. This suggests that CD-MOFs have the potential to encapsulate various types of drugs by considering the hydrophobicity and hydrophilicity of both the pores and the drug molecules. Our previous studies have revealed that CD-MOFs exhibit variations in encapsulated pores depending on the hydrophobicity or hydrophilicity of the drugs [1]. However, for CD-MOFs to be more effectively utilized as drug carriers, it is necessary to quantitatively evaluate the amphiphilic pores of CD-MOFs and their encapsulation potential and interactions with various drugs.
In this study, we aimed to identify key factors in drug encapsulation within CD-MOFs using molecular simulations. Previously, solvent effects were not incorporated into simulations, which limited quantitative comparisons between experimental and simulation results. By employing the Widom insertion method, we confirmed the feasibility of incorporating solvent effects into simulations. Additionally, molecular simulations were performed for 26 anticancer drugs with different hydrophobicity and molecular weights to evaluate their loaded amounts and the distribution of encapsulated drugs among different pores in CD-MOFs. Multiple regression analysis was also conducted on these results to extract key drug properties, thereby attempting to elucidate the key factors of drug encapsulation within the amphiphilic pores of CD-MOFs.
Refference
[1] A. Ohashi, K. Ohshima, S. Ohsaki, H. Nakamura, S. Watano, Application of cyclodextrin-based metal-organic frameworks for multi-drug carriers: A combined experimental and simulation study, Int J Pharm 670 (2025) 125104. https://doi.org/10.1016/j.ijpharm.2024.125104.
