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

Carbohydr Polym. 2019 Jul 15:216:224-230. doi: 10.1016/j.carbpol.2019.04.037. Epub 2019 Apr 9.

Abstract

γ-Cyclodextrin-based metal-organic framework (γCD-MOF) crystals were successfully synthesized using a vapor diffusion method. An applicability of γCD-MOF for encapsulation of immunosuppressive disease-modifying antirheumatic drug leflunomide (LEF) was examined. Loading of LEF in γCD-MOF was performed by impregnation and co-crystallization. The empty and loaded γCD-MOFs were characterized using X-ray powder diffraction, N2 adsorption/desorption, thermogravimetric analysis, 1H NMR and FTIR spectroscopy. It was shown that in the presence of γCD-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 γCD-MOF has improved pharmacologically relevant properties such as solubility, dissolution rate and membrane permeability. It can be proposed that γCD-MOF can be considered as novel strategy for delivery of leflunomide.

Keywords: Cyclodextrin-based metal-organic framework; Dissolution; Leflunomide; Permeability; Solubility; Teriflunomide.

MeSH terms

  • Antirheumatic Agents / chemistry*
  • Crotonates / chemical synthesis*
  • Drug Liberation
  • Hydroxybutyrates
  • Kinetics
  • Leflunomide / chemistry*
  • Metal-Organic Frameworks / chemical synthesis
  • Metal-Organic Frameworks / chemistry*
  • Nitriles
  • Oxidation-Reduction
  • Permeability
  • Porosity
  • Prodrugs / chemistry*
  • Solubility
  • Toluidines / chemical synthesis*
  • gamma-Cyclodextrins / chemical synthesis
  • gamma-Cyclodextrins / chemistry*

Substances

  • Antirheumatic Agents
  • Crotonates
  • Hydroxybutyrates
  • Metal-Organic Frameworks
  • Nitriles
  • Prodrugs
  • Toluidines
  • gamma-Cyclodextrins
  • teriflunomide
  • Leflunomide
  • gamma-cyclodextrin