Sonochemical synthesis of -CD-MOFs microcapsule for myricetin delivery: Study of adsorption mechanism, molecular simulation, solubility, antioxidation, biocompatibility, and in vitro digestion

Improving the bioavailability of myricetin and thus enlarging its commercial utilization have always been highly desirable. gamma-cyclodextrin (gamma-CD) based metal organic frameworks (gamma-CD-MOFs) has provided novel technological opportunities for pharmaceutical and nutraceutical delivery, as credited by its recognized adsorption property and renewable nature. Here, we proposed a facile way of preparing uniform gamma-CD-MOFs with mono-dispersity (14.24 +/- 1.39 mu m) and high-yield (84.74 +/- 2.30%) by using ultrasonic-assisted synthetic method for myricetin loading and delivery. The generated gamma-CD-MOFs showed excellent loading capacity via stepwise adsorbing myricetin within its diverse pores. Adsorption kinetics analysis confirmed the significance of chemisorption effects during the adsorption process, and diffusion model was utilized to clarify the diffusion profile of myricetin into gamma-CD-MOFs in detail. The tandem of experimental (SEM, XRD, DSC, TG, BET, FT-IR) and computational (MD simulations) approaches allowed us to identify the presence status and intermolecular interactions of encapsulated myricetin, as well as the adsorption mechanism. gamma-CD-MOFs displayed superior capacity to solubilize myricetin as reflected by the enhanced solubility and dissolution rate in comparison to the single gamma-CD encapsulation. The improved solubility also considerably contributed to the enhanced antioxidant activity of myricetin-loaded gamma-CD-MOFs. In vitro digestion simulation and cell cytotoxicity results further showed that gamma-CD-MOFs encapsulation could achieve controlled release of myricetin with satisfactory bioavailability. This work highlights a facile way for constructing cyclodextrin-based MOFs and prompting further practical application of myricetin or other hydrophobic nutrients.