Development of Thermal-Responsive Carboxymethylcellulose-Based Hydrogel Embedded with Fe-Based MOFs for Controlled Flutamide Release

This study investigates a novel dual-functional drug delivery system utilizing Flutamide-loaded Fe₃O₄-doped Mil-100(Fe) nanoparticles embedded within a carboxymethyl cellulose (CMC) hydrogel, designed for magnetically triggered hyperthermia and controlled drug release. Fe₃O₄-doped Mil-100(Fe) and unmodified Mil-100(Fe) NPs were synthesized, characterized by SEM, XRD, and EDX, and subsequently loaded with Flutamide. Then, the synthesized NPS were integrated with CMC hydrogels. The final hydrogels were evaluated from the viewpoint of water uptake, porosity, degradation, cytotoxicity, drug release, and kinetic study. The Fe₃O₄-doped Mil-100(Fe) NPs exhibited higher drug loading capacity (26 ppm vs. 6 ppm) and enhanced porosity compared to unmodified NPs. CMC hydrogels incorporating these NPs displayed increased water uptake (>500%) and porosity, with Fe₃O₄-doped NPs showing a more significant impact. Degradation studies revealed similar trends for both NP-loaded hydrogels, although Fe₃O₄-doped NPs exhibited a slightly higher degradation rate (80%). MTT assays confirmed the biocompatibility of all hydrogel formulations, with cell viability exceeding 89%. Drug release studies, conducted under both physiological and alternating magnetic field (AMF) conditions, demonstrated Fickian diffusion kinetics for hydrogels. Fe₃O₄-doped NPs exhibited faster and more sustained Flutamide release, attributed to their higher loading capacity and porosity. AMF application slightly enhanced release rates, although the predominant control remained diffusion-limited. This work demonstrates the potential of Fe₃O₄-doped Mil-100(Fe) NPs within CMC hydrogels for targeted, magnetically triggered drug delivery and hyperthermia-based cancer therapy.