Crystal Engineering Strategy for Prevention of Hepatotoxicity

Grant Winners

Dean

Abstract

Drugs are an important cause of liver toxicity. More than 900 drugs, and natural products have been reported to cause liver toxicity, and drugs account for 20-40% of all instances of fulminant hepatic failure. Drug-induced hepatic injury is the most common reason cited for withdrawal of an approved drug. Silibinin (commercially available and safe natural product), in animal experiments has been shown to protect rat or mouse liver against the toxic effects of many drugs and hepatotoxicants. These beneficial effects have been attributed to the antioxidant and membrane stabilizing effects of the compound. In this study, two model drugs, acetaminophen and amiodarone that are known to cause liver toxicity, will be evaluated to form cocrystals with silibinin. We anticipate that these cocrystals will be beneficial in preventing liver injury. We will explore several strategies (mechano and sonochemical methods) to make cocrystals of both the aforementioned drugs with silibinin. The resulting cocrystals will be thoroughly characterized and their efficacy in offering protection against the liver toxicity of acetaminophen and amiodarone will be determined in liver specific cell lines (HepG2 and Hep3B).