Synthesis and in vitro evaluation of cross-linked tragacanthin nanofibers as implants for delivery of cisplatin to hepatocellular carcinoma

Abstract

There is growing interest in the use of electrospun polymeric nanofibers in drug delivery systems due to their remarkable surface-to-volume ratio, which enhances the processes of drug loading, specific cell binding and proliferation. The preferred polymers for drug delivery must be biocompatible and biodegradable. Gum tragacanth is one of the materials of choice for drug delivery. This work aimed at cross-linking the tragacanthin, the water-soluble fraction of gum tragacanth, with glutaraldehyde, synthesis of the cross-linked nanofibers and evaluating their properties to encapsulate and deliver a drug using caffeine as a model drug in the first place. The nanofibers were then loaded with cisplatin and evaluated against HepG2 cell line. The drug-loaded nanofibers (dia. 0.841 μm) were prepared by electrospinning using glutaraldehyde as the cross-linker and glycerol as a plasticizer and characterized by scanning electron microscopy, Fourier transform-infrared spectroscopy, electronic spectroscopy, 1HNMR, powder X-ray diffraction analysis, and thermogravimetric analysis. They released the encapsulated drugs in a sustained manner at pH 7.4 over 4.5 days (∼275 h with ∼80 % release) following Higuchi (cisplatin) and Hixon-Crowell (caffeine) kinetics. In a cytotoxicity assay against HepG2 cell line the cisplatin-loaded nanofibers exhibited enhanced activity compared to that with the standard cisplatin and in the caspase activity assay it activated caspase 3 to a higher extent and 8 and 9 to double the extent (4-fold) of cisplatin, suggesting a higher apoptotic activity by the nanoformulation than the standard cisplatin. Thus, nanoformulation appeared to be a potential candidate for treating hepatocellular carcinoma as an implant.