Facile preparation of dual pH/thermo-responsive MOF@chitosan hydrogel microspheres through reactive spray drying for sustained curcumin release and enhanced hemostasis.

In this study, a temperature and pH-sensitive hydrogel microsphere based on metal-organic frameworks (MOFs) and chitosan was successfully prepared through a simple and scalable reactive spray drying technology. Specifically, chitosan quaternary ammonium salt (HACC) and metal organic framework NH₂-MIL-53 were selected as raw materials, citric acid was used as the crosslinker, and MOF@Chitosan composite hydrogel microspheres were prepared by reactive spray drying. During the spray drying process, chemical crosslinking was primarily formed through the reaction between the hydroxyl and amino groups of HACC and the carboxyl group of citric acid. The conditions for forming microspheres were optimized, and the prepared microspheres and their raw materials were characterized using analysis methods such as Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray photoelectron spectroscopy. Next, curcumin was selected as the model drug to explore the controlled release and hemostatic properties of the microspheres. Research indicates that these microspheres are sensitive to pH and temperature, and their drug release rate is pH dependent. The drug release process conforms to a first-order kinetic model. Cell viability assay, in vitro coagulation index assay, and hemostasis tests have demonstrated that these microspheres exhibit excellent cell compatibility and promote hemostasis. These microspheres possess excellent sustained-release performance, cellular compatibility, and hemostatic properties, making them promising for widespread application in multifunctional drug delivery systems.