Organic-inorganic hybrid based on Laponite as a platform for controlled release of 5-fluorouracil

Abstract Nanoclays such as Laponite are promising drug carriers due to their layered structure and biocompatibility; however, their performance is often limited by challenges such as clay aggregation, burst or uncontrolled drug release. To address these limitations, we synthesized an organic–inorganic hybrid by grafting (3-aminopropyl)triethoxysilane (APTES) onto Laponite, enhancing its capacity to load and control release of the anticancer drug 5-fluorouracil. Structural characterization by FTIR shows the presence of APTES functional groups, later confirmed to the covalently bound with Laponite using 29 Si MAS NMR. In addition, pXRD and SAXS reveal the interlayer increase, indicating the preference of the modification on the interlayer surface and the drug incorporation as well. Also, SEM revealed a morphology change from smooth pristine Laponite to a rougher hybrid surface, evidencing a reorganization of the layered framework and the formation of a hybrid material, instead of a functionalization. With TGA we estimate the amount of APTES incorporated to be around 19.2% the initial mass of Laponite, and N 2 adsorption reveals the decrease of the specific surface area from 359 to 202 m 2 ·g −1 . The hybrid exhibited improved 5-FU loading (36%) compared to pristine Laponite (22%) and suggested a slower, diffusion-driven, pH-responsive release favoring acidic tumor-like environments. Biocompatibility assays indicated low cytotoxicity and reduced irritant potential upon drug incorporation. These findings suggest that the Laponite–APTES hybrid is a versatile platform for controlled, stimuli-responsive drug delivery, with potential applications in cancer therapy. Graphical Abstract