Nanothymoquinone, a novel hepatotargeted delivery system for treating CCl₄ mediated hepatotoxicity in rats
2013
Verma, Shashi Kant | Rastogi, Shweta | Javed, Kalim | Akhtar, Mohd | Arora, Indu | Samim, Mohd
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 (NTQL), 1.25 (NTQM) and 12.5 (NTQH) 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 NTQH 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.
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