Novel metal organic frameworks improves solubility and oral absorption of mebendazole: Physicochemical characterization and in vitro-in vivo evaluation

Abstract

We aimed to synthesize Zeolitic Imidazolate Framework (ZIF-8) at milieu conditions in a hydrated environment. In this work, the aptness of ZIF-8 as a budding carrier system for delivery of an anti-parasitic drug, Mebendazole was examined. Mebendazole was loaded sedentary into the ZIF-8 fragments at the time of assimilation using the impregnation approach. After the synthesis of ZIF-8, these were subjected to physicochemical characterization techniques such as FTIR, PXRD, DSC, FE-SEM, and TEM. PXRD confirmed the structural integrity of ZIF-8 and it did not reveal any change in its structure after encapsulation of MBZ. FE-SEM and TEM micrographs of pure ZIF-8 revealed the formation of hexagonal nanoclusters with built facets which were in the size range of 100–150 nm. The triumphant impregnation of the drug, i.e. MBZ upon the surface of ZIF-8 was validated by UV–Visible and FTIR spectroscopy studies. Solubility studies showed 11 fold enhancement in solubility of MBZ@ZIF-8 in comparison to the free drug (104.4 ± 17.880 v/s 10.92 ± 1.984). In vitro release studies showed ∼80% ± 8.89 drug release in 24 h in a buffer solution (pH 6.8). Thereafter, in vivo pharmacokinetic studies exhibited approximately four-fold enhanced bioavailability (AUC0-ꝏ 134.256 ± 26.91 v/s 34.628 ± 6.92), and six-fold improved distribution half-life (6.142 ± 1.22 v/s 1.00 ± 2.00). Therefore, metal-organic frameworks could be a potential strategy to improve the biopharmaceutical attributes of hydrophobic drugs.