期刊
出版社
ELSEVIER
DOI: 10.1016/j.msec.2020.110774
关键词
Bioavailability; Biorelevant media; Dissolution; Metal-organic frameworks; Methotrexate; Permeability
资金
- Russian Foundation for Basic Research [18-29-04023]
In this work, metal-organic frameworks on the basis of y-cyclodextrin (gamma CD-MOF) were proposed as carriers for methotrexate (MTX) which is widely used as chemotherapy agent and immune system suppressant. The synthesized gamma CD-MOF was loaded with MTX by impregnation and co-crystallization. The obtained composites were characterized using powder X-ray diffraction, N-2 adsorption/desorption, FTIR spectroscopy, solid-state C-13 MAS CP/TOSS NMR and scanning electron microscopy. Pharmaceutically relevant properties of MTX alone and loaded in gamma CD-MOF were investigated in vitro and in vivo. The faster dissolution of MTX incorporated in gamma CD-MOF was demonstrated in blank buffers and biorelevant media (FaSSGF, FaSSIF) simulating the gastrointestinal fluids. Inclusion complex formation of MTX with gamma-CD enhances the drug dissolution rate and, at the same time, slightly decreases the drug permeability through the lipophilic membrane. The in vivo experiments showed the improved pharmacokinetic parameters of MTX loaded in gamma CD-MOF.
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