Zeolitic Imidazolate Framework-8 (ZIF-8) as a Carrier for Kaempferol Delivery to Protect Against Gamma Radiation-Induced Mortality and Damage

Background/Objectives: Kaempferol (KAE) is used to treat gamma radiation-induced damage. However, poor water solubility of KAE restricts its application. Therefore, we developed a KAE-loaded zeolitic imidazolate framework-8 (KAE@ZIF-8) to improve the solubility and bioavailability of KAE, thereby enhancing the radioprotective effect against gamma radiation. Methods: The composite was characterized using scanning electron microscopy (SEM), nitrogen adsorption/desorption analysis, X-ray diffraction (XRD), differential scanning calorimetry (DSC), equilibrium solubility assessments, in vitro release studies, stability evaluations, and drug-loading capacity measurements. The cytotoxic effects of KAE@ZIF-8 on Caco-2 cells were assessed in vitro. Meanwhile, the bioavailability of the preparation was also investigated. Finally, the protective efficacy of KAE@ZIF-8 against total body irradiation was evaluated in C57BL/6 mice. Results: The results indicated that KAE@ZIF-8 was successfully constructed, exhibiting a uniform hexagonal crystal morphology, with KAE transitioning from a crystalline to an amorphous state. As a carrier, ZIF-8 significantly enhanced the solubility of KAE by 9.2-fold, and the cumulative release within 12 h reached approximately 89%. Meanwhile, ZIF-8 could significantly enhance the bioavailability of KAE and reduce its toxicity. We found that pretreatment with KAE@ZIF-8 prolonged mouse survival time after 9 Gy total body irradiation (TBI). Mice were scarified on the 7th day after 7 Gy TBI. Results showed that KAE@ZIF-8 exhibited an improvement of the radioprotective effects, including weight loss mitigation, spleen index increase, radiation-induced intestinal injury attenuation, and modulation expression of IL-1β, IL-6, TNF-α and TGF-β1 following radiation. Conclusions: These results suggest the potential effect of ZIF-8 as an oral drug delivery carrier for radioprotective drugs.