Delivery of Eicosapentaenoic Acid-Loaded Cellulose Nanocrystal Alleviates Liver Fibrosis Via Modulating Phospholipids and Apoptotic Regulators

Liver fibrosis is a chronic liver condition that can eventually lead to cirrhosis. Eicosapentaenoic acid (EPA, C20:5n-3), has shown promise in alleviating liver injury. However, its delivery to the liver can be challenging. In this study, we aimed to prepare EPA-loaded cellulose nanocrystal (CNC) with high entrapment efficiency and sustained release of EPA and tested its potential therapeutic effect on a murine Diethylnitrosamine (DEN)induced fibrosis model. The results demonstrated that EPA, either in its free form or encapsulated, was effective in ameliorating liver fibrosis and reducing collagen deposition compared to the non-treated group. Specifically, the encapsulated form of EPA was highly effective in reducing oxidative markers such as Malondialdehyde (MDA) and Advanced Oxidation Protein Products (AOPP), as well as the fibrosis-related biomarker AlphaFetoprotein (AFP). Additionally, the administration of EPA to the DEN-induced fibrosis groups resulted in a significant modulation in membrane phospholipids, potentially improving membrane stability and function. Our findings reveal that EPA may be effective in reducing fibrosis development by targeting various molecular pathways. This includes reducing the expression of beta-catenin, CD95, and Bcl-2 and downregulating miR-221, which is involved in fibrosis progression. This study highlights the potential of EPA-encapsulated CNC as a safe and effective approach for managing liver fibrosis.