Bile acid-based polydrug nanoparticles for the treatment of acute liver injury

Acute liver failure and non-alcoholic fatty liver disease (NAFLD) are a common chronic liver disease worldwide, causing tremendous clinical burden. Despite the increasing prevalence of these life-threatening liver damages, effective medical treatment has not been established. Here, we developed a new treatment strategy based on ursodeoxycholic acid (UDCA) which is one of bile acids and effective for the liver diseases. We designed poly(ursodeoxycholic acid-oxalate) (PUOX) as a polymer prodrug of UDCA. PUOX has hydrogen peroxide (H₂O₂)-scavenging peroxalate ester bonds and could be formulated into nanoparticles. PUOX nanoparticles released UDCA in a H₂O₂-triggered manner and exerted concurrent antioxidant and anti-inflammatory effects with cytoprotective actions. In mouse models of acute liver failure and NAFLD, PUOX nanoparticles exerted highly potent therapeutic effects without noticeable toxicity. PUOX nanoparticles could be a promising approach to improve the efficacy for various H₂O₂-associated liver disease. Graphical abstract: Poly(ursodeoxycholic acid-oxalate) (PUOX) is a H₂O₂-responsive polymeric prodrug of UDCA. PUOX nanoparticles exert potent cytoprotective effects in liver diseases such as fatty acid and drug-intoxicated acute liver failure. (Figure presented.)