A nanoformulation of cisplatin with arabinoxylan having enhanced activity against hepatocellular carcinoma through upregulation of apoptotic and necroptotic pathways

Abstract

Cisplatin is a versatile drug used to treat various types of cancer, but it is associated with high toxicity and resistance problems. Several approaches, including nanotechnology, have been adopted to minimize the toxic effects and to overcome the resistance of cisplatin. Most of the nanoformulations involve the use of synthetic or semisynthetic polymers as drug carriers. In this study arabinoxylan nanoparticles have been investigated as drug reservoirs for intestinal drug delivery. The drug-loaded arabinoxylan nanoparticles (size: ∼1.8 nm, polydispersity index: 0.3 ± 0.04) were prepared and nanoformulation was characterized by various analytical techniques. The nanoformulation was found to be stable (zeta potential: 31.6 ± 1.1 mV). An in vitro cytotoxicity against HepG2 and HEK 293 cell lines was studied. The cell viability analysis showed greater efficacy than the standard cisplatin (IC50: cisplatin 2.4, arabinoxylan nanoformulation 1.3 μg mL−1). The expression profile of carcinogenic markers revealed a six-fold upregulation of MLKL and 0.9-fold down regulation of KRAS, suggesting the activation of the necroptotic pathway by the drug-loaded nanoparticles. The nanoformulation exhibited a sustained release of cisplatin with a cumulative release of ∼40 % (at pH 7.4) and ∼30 % (at pH 5.5) over a period of 12 h with very low initial burst. The study suggests that the use of the new nanoformulation can significantly reduce the required dose of cisplatin without compromising efficacy and more efficient release at basic pH.

Keywords

• Hepatocellular carcinoma
• Nanomedicine
• Arabinoxylan
• Hemicelluloses
• Gene expression