Formulation of pH-sensitive ZIF-8 (MOF) impregnated amino-chitosan biocomposite beads for sustained release of 5-fluorouracil

Abstract

pH-sensitive carriers have emerged as an optimal choice for the oral administration of anticancer drugs, exhibiting the desired release performance. This study aims to develop biocomposite beads for the sustained release of the anticancer drug 5-fluorouracil (5-FU). Here, 5-FU was encapsulated within a ZIF-8 metal-organic framework (MOF), which was subsequently impregnated into amino-chitosan beads. The resulting Am-CS@ZIF-8 biocomposite beads were characterized for their chemical structure, surface morphology, elemental composition, crystallinity, surface charges, and mechanical properties utilizing Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), zeta potential analysis, and a texture analyzer, respectively. The developed beads exhibited a textured surface, denser composition, and a positively charged surface with a maximum zeta potential of +12.4 at pH 7.4. In comparison to Am-CS beads, the Am-CS@ZIF-8 biocomposite beads demonstrated superior mechanical properties, achieving a maximum stress value of 5.668 MPa compared to the 1.874 MPa recorded for pure Am-CS beads. pH sensitivity was assessed through the investigation of water uptake behavior at pH 1.2 and pH 7.4. The Am-CS@ZIF-8 biocomposite beads demonstrated a high encapsulation efficiency of approximately 81.6 % for 5-FU. They exhibited pH-responsive release behavior, with only 17 % of the drug released at pH 1.2 after 2 h and a sustained release of 52 % at pH 7.4 over 24 h. The release mechanism was predominantly governed by Fickian diffusion, as closely fitted by the Peppas-Sahlin kinetic model. The formulated carrier confirmed its biodegradability under enzymatic physiological conditions, suggesting its potential applicability as an effective system for the oral delivery of anticancer drugs.