Smart MOF-integrated biopolymeric hydrogel systems as a novel strategy for sustained anticancer drug delivery

The development of localized and sustained drug delivery systems remains a critical challenge in glioblastoma therapy due to rapid drug clearance and systemic toxicity. In this study, a smart hybrid delivery platform was engineered by integrating amino-functionalized iron-based metal–organic frameworks (NH₂-MIL-88B(Fe)) into dual-crosslinked sodium alginate/polyvinyl alcohol hydrogel thin films for controlled 5-fluorouracil (5-FU) delivery. The resulting composite films exhibited high hydrophilicity and structural stability, supporting efficient drug accommodation and diffusion regulation. Comprehensive physicochemical characterization confirmed uniform incorporation of the porous framework within the polymeric network, yielding a mesoporous architecture with an average pore size of ∼2.75 nm and a specific surface area of ∼17.322 m²/g. The system achieved a high encapsulation efficiency (up to 92.18 %) and demonstrated sustained, non-burst drug release, reaching ∼78.4 % cumulative release over 120 h under physiological conditions, with kinetics consistent with diffusion-dominated non-Fickian transport. In vitro cytotoxicity studies using U-87 glioblastoma cells revealed enhanced anticancer activity with moderated toxicity relative to burst-release free 5-FU, indicating effective therapeutic performance with improved biocompatibility. These findings establish the MOF–hydrogel hybrid thin-film system as a promising localized delivery platform for glioblastoma treatment.