Poly(lactic‐co‐glycolic acid)‐albumin nanoparticles for targeted delivery of capsaicin in alleviating non‐alcoholic fatty liver disease: In vitro study

Abstract Globally, 20%–30% of people are affected by Non‐Alcoholic Fatty Liver Disease (NAFLD). Currently, there is no approved drug for the treatment of NAFLD. It is mostly asymptomatic and is characterized by the accumulation of fat in the liver without excessive alcohol consumption. Capsaicin, a nutraceutical with anti‐lipogenic and anti‐inflammatory properties, is a promising candidate for NAFLD management. However, its poor bioavailability and potential gastrointestinal irritation limit its clinical utility. To overcome these challenges, capsaicin was encapsulated in a dual delivery system using poly(lactic‐co‐glycolic acid) and bovine serum albumin. This system was developed using nanoprecipitation methods to enhance stability, liver targeting, and therapeutic efficacy of capsaicin. Additionally, the inclusion of albumin helps combating hypoalbuminemia, a condition commonly observed in NAFLD cases. Albumin interacts with hepatic‐specific receptors like the asialoglycoprotein receptor and GP60, which are predominantly expressed on liver cells, enhancing the specificity of albumin‐based nanoparticles for liver uptake. Nanoparticles were optimized for capsaicin loading and tested in HepG2 cells‐induced NAFLD models. Capsaicin nanoparticles significantly reduced intracellular triglycerides, achieving 89% for lipid reduction in a dose‐dependent manner. This dual nanoformulation demonstrates a platform for liver‐targeted capsaicin delivery, addressing limitations of conventional therapies and offering a promising therapeutic approach.