Insight into the Loading Properties of Na+ Green-Functionalized Clinoptilolite as a Potential Carrier for the 5-Fluorouracil Drug, its Release Kinetics, and Cytotoxicity

Abstract

Herein, natural zeolite (clinoptilolite) was functionalized by Na+ ions (G.Na+/Clino) utilizing a green tea extract prepared by a green production method as a potential carrier for the 5-fluorouracil (5-Fu) drug with enhanced physicochemical behaviors. The G.Na+/Clino-modified product showed enhanced surface area (312 m2/g) and ion-exchange capacity (387 mequiv/100 g). The loading studies reflect high and controlled loading properties of G.Na+/Clino with an actual loading capacity of 291 and 462 mg/g, respectively. The loading reactions of 5-Fu into G.Na+/Clino were of pseudo-second-order kinetics and exhibited Langmuir isotherm properties. This suggested a monolayer and homogeneous loading process by chemical complexation and ion-exchange mechanisms with a Gaussian energy value of 10.47 kJ/mol. Additionally, these reactions were of endothermic and spontaneous nature based on the determined thermodynamic parameters. The release studies demonstrated the 5-Fu release profile for about 150 h at pH 1.2 and for 80 h at pH 7.4. The release reactions had non-Fickian transport properties and were controlled by both erosion and diffusion mechanisms, considering the release kinetic findings and the values of the diffusion exponent (0.42 at pH 1.2 and 0.37 at pH 7.4). The composite showed remarkable biocompatibility based on the measured cell viability and a cytotoxic effect on normal colorectal cells (CCD-18Co). Additionally, the application of G.Na+/Clino as an inorganic carrier for the 5-Fu drug prompted the cytotoxic effect of the drug on colon cancer cell treatment (HCT-116).