Improving the genistein oral bioavailability via its formulation into the metal–organic framework MIL-100(Fe)

International audience; Despite the interesting chemopreventive, antioxidant and antiangiogenic effects of the natural bioflavonoid genistein (GEN), its low aqueous solubility and bioavailability make it necessary to administer it using a suitable drug carrier system. Nanometric porous Metal-Organic Frameworks (nanoMOFs) are appealing systems for drug delivery. Particularly, the mesoporous MIL-100(Fe) possesses a variety of interesting features related to its composition and structure, which make it an excellent candidate to be used as a drug nanocarrier (highly porous, biocompatible, can be synthetized as homogenous and stable nanoparticles (NPs), etc.). In this study, GEN was entrapped by simple impregnation in MIL-100 NPs achieving a remarkable drug loading (27.1 wt%). A combination of experimental and computing techniques was used to achieve a deep understanding of the encapsulation of GEN in MIL-100 nanoMOF. Subsequently, GEN delivery studies were carried out under simulated physiological conditions, showing on the whole a sustained GEN release for 3 days. Initial pharmacokinetics and biodistribution studies were also carried out upon the oral administration of the GEN@MIL-100 NPs in a mouse model, evidencing a higher bioavailability and showing that this oral nanoformulation appears very promising. To the best of our knowledge, the GEN-loaded MIL-100 will be the first antitumor oral formulation based on nanoMOFs studied in vivo, and paves the way to efficiently deliver nontoxic antitumorals by a convinient oral route. .