Green Synthesis of Glabridin‐Loaded Zeolitic Imidazolate Framework‐8 Drug Delivery System: Characterization, Synergistic Antibacterial Efficacy, and pH‐Dependent Drug Release Kinetics

ABSTRACT This study reports a green one‐pot synthesis of glabridin‐loaded Zeolitic Imidazolate Framework‐8 (Glab@ZIF‐8) drug delivery system (DDS) with exceptional drug loading encapsulation (DLE) of ≈ 98.7% and drug loading capacity (DLC) of 32%, surpassing values reported in previous ZIF‐8‐based DDS. Characterizations using Fourier‐transform infrared (FTIR), UV–Visible spectroscopy, dynamic light scattering (DLS), and X‐ray diffraction (XRD) confirmed successful encapsulation of Glab within ZIF‐8 while preserving its crystallinity. Glab@ZIF‐8 exhibited a hexagonal morphology with increased particle size (138.6 ± 5.4 nm) and a higher zeta potential (+41.9 mV), suggesting enhanced colloidal stability and efficient drug entrapment. Thermogravimetric analysis (TGA) demonstrated a total of 32.1% decomposition of Glab@ZIF‐8 up to 644 °C. Antibacterial assays revealed that Glab@ZIF‐8 exhibited superior activity against Staphylococcus aureus (inhibition zone: 26.2 ± 0.3 mm) and Escherichia coli (23.3 ± 0.2), comparable to that of ampicillin. The minimum inhibitory concentration (MIC) was determined to be 32.5 μg/100 μL. Furthermore, the time‐kill studies confirmed a dose‐ and time‐dependent antibacterial effects of Glab@ZIF‐8. In vitro drug release studies showed strong pH‐ and temperature‐responsive behavior, with a cumulative release of 93.7% ± 2.4% release at pH 5 (at 37°C) over 72 h. The Glab@ZIF‐8 system thus combines high drug loading efficiency, excellent antibacterial activity, and tuneable release characteristics, highlighting its potential as a promising DDS for combating drug‐resistant infections.