Abstract / Summary
Zeolitic imidazolate frameworks (ZIFs), a class of metal–organic frameworks (MOFs), have emerged as promising carriers in recent years. The characteristics of ZIF-8 are highly sensitive to various synthesis parameters. Many studies examined these parameters by adjusting only one factor at a time, thus overlooking their combined effects. Our work focused on a systematic approach of design of experiments (DOE)/extreme gradient boosting (XGBoost)-assisted development of crocin-loaded ZIF-8 nanoparticles (NPs). The optimum formulation was synthesized at 45 °C using a 2-MeIM:Zn(NO 3 ) 2 ratio of 2.7 and a stirring speed of 100 rpm for 3.5 h. The effects of the crocin:NPs ratio and sonication time on entrapment efficiency (EE) were also evaluated. The ZIF-8@crocin was analyzed by FESEM-EDX, BET, FTIR, XRD, TGA, and DTG. The 1:1 crocin:ZIF-8 ratio showed the highest EE% of 61.8 and a controlled release profile. We also used molecular dynamics (MD) simulations to understand drug incorporation and release at the molecular level. The sorption of an average of 41 crocin molecules per cell (50 wt%) on the surface of ZIF-8 NPs was confirmed by configurational-bias grand canonical Monte Carlo (CB-GCMC) simulations. The mean square displacement (MSD) analysis under dry conditions yielded values of 7.18 × 10 −5 and 4.57 × 10 −5 for 10 4 and 10 5 steps, respectively. In an aqueous environment, the MSD was also equal to 3.54 × 10 −5 . The reduced slope trendline represented slow drug release by a decreased self-diffusion coefficient in the aqueous environment. The molecular docking and MD simulations were aligned with the experimental data.