Nanostructure-mediated drug delivery is known to have a potential to improve drug bioavailability, apart from fostering release deviation of drug molecules and enabling precision drug targeting. Solid lipid nanoparticles (SLNs) have drawn great deal of the attention of scientists in finding a solution to minimize pharmaceutic limitations of the drugs used. Silymarin (Sm) has so far been used for treating diverse liver and gallbladder disorders, such as cirrhosis, hepatitis, and jaundice, and for protecting the liver against poisoning from chemical and environmental toxins on account of its antihepatotoxic and antioxidative properties. The present study aims to develop a novel silymarin-loaded solid lipid nanoparticle (Sm-loaded SLN) system with enhanced bioavailability and with an ability to provide excellent hepatic protection for poorly water-soluble drugs. Based upon our investigation results with apoptotic markers, PCNA and lightmicroscopic findings, it can be concluded that Sm-loaded SLN significantly reduced D-GaIN/TNF-alpha-induced hepatotoxicity, which suggested improved bioactivity compared to Sm. In conclusion, Sm-loaded SLN could be a useful system for the delivery of poorly water-soluble Sm, apart from providing favourable hepatic protection. (C) 2014 Elsevier Ltd. All rights reserved.