Synthesis of Biocompatible Nanoporous ZIF-8-Gum Arabic as a New Carrier for the Targeted Delivery of Curcumin.

ABSTRACT

The synthesis of biocompatible nanoporous zeolitic imidazolate framework-8 (ZIF-8) was performed in the presence of gum arabic (GA), curcumin (CCM), and folic acid (FA) as a template for the biomineralization process, a natural anticancer component, and a targeting agent, respectively. The synthesis of ZIF-8-GA-CCM-FA was completed in a single step at room temperature in aqueous media with a minimum amount of ethanol at a linker/metal molar ratio of 10. FA was dissolved by the alkaline medium produced by a 2-methyl imidazolium (HmIm) linker without using any toxic organic solvent or additional conjugation agents. The FA-modified carrier can target the folate receptors on Hela cells. To the best of our knowledge, this is the first report about the one-pot encapsulation of CCM and FA in a biocompatible ZIF-8-GA framework in a green solvent. This method enables high CCM loading in the ZIF-8-GA framework structure (ca. 90%) at a short time of 15 min. The effect of CCM concentration was investigated on the size, morphology, and crystallinity of the synthesized structures. The products were characterized with field emission scanning electron microscopy, Brunauer-Emmett-Teller surface area analysis, X-ray diffraction, Fourier transform infrared, and UV-vis spectroscopy techniques. The release rate of CCM from ZIF-8-GA-CCM-FA was studied at different pH values. In vitro drug release of CCM was higher in the acidic medium (pH 5.5, 6.5) compared to physiological pH (7.4). The cytotoxicity of ZIF-8-GA, ZIF-8-GA-CCM, and ZIF-8-GA-CCM-FA structures was evaluated by the standard 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on the three cell lines (fibroblast (normal cell), Hela (FR-positive), and A549 (FR-negative). These results suggested that the ZIF-8-GA-CCM-FA framework can have a promising effect on the targeted treatment of cancer cells.