γ-Cyclodextrin-metal organic frameworks as efficient microcontainers for encapsulation of leflunomide and acceleration of its transformation into teriflunomide

gamma-Cyclodextrin-based metal-organic framework (gamma CD-MOF) crystals were successfully synthesized using a vapor diffusion method. An applicability of gamma CD-MOF for encapsulation of immunosuppressive disease-modifying antirheumatic drug leflunomide (LEF) was examined. Loading of LEF in gamma CD-MOF was performed by impregnation and co-crystallization. The empty and loaded gamma CD-MOFs were characterized using X-ray powder diffraction, N-2 adsorption/desorption, thermogravimetric analysis, H-1 NMR and FTIR spectroscopy. It was shown that in the presence of gamma CD-MOF leflunomide is transformed into its pharmacologically active form - teriflunomide that can be also applied alone in the treatment of multiple sclerosis. It was demonstrated that teriflunomide released from gamma CD-MOF has improved pharmacologically relevant properties such as solubility, dissolution rate and membrane permeability. It can be proposed that gamma CD-MOF can be considered as novel strategy for delivery of leflunomide.