Nanothymoquinone, a novel hepatotargeted delivery system for treating CCl4 mediated hepatotoxicity in rats

Abstract

Thymoquinone (TQ) is the major active principle of Nigella sativa (N. sativa) which is widely being used as a hepatoprotective agent nowadays. However, toxicity at high doses with poor water solubility limit its usage as a therapeutic agent. The idea behind the present study is to design a nanocarrier that exploits the benefit of the antioxidant property of TQ without any toxicity. For this purpose, PAG (p-aminophenyl-1-thio-β-D-galactopyranoside) coated NIPAAM (N-isopropyl acrylamide) nanoparticles are synthesized followed by encapsulation of TQ (NTQ) in their hydrophobic core. PAG is a ligand which directly interacts with asialoglycoprotein receptors (ASGP-R) present on the surface of hepatocytes and delivers the drug directly to the liver. NTQ have a size of ∼100 nm and were characterized using IR, NMR, DLS, and TEM. The drug was given in two modes: one as NTQ (3 groups: 0.125 (NTQ_L), 1.25 (NTQ_M) and 12.5 (NTQ_H) μg kg⁻¹ body weight, intraperitoneal (i.p.)) and the other as TQ (12 500 μg kg⁻¹ body weight, i.p.). The best results were obtained with NTQ_H which is around 1000 times lower than TQ in concentration. Serum and biochemical parameters followed by restoration of histopathology supported this. Expression of inflammatory enzyme COX-2 and NF-kB also gave evidence in support.