Redox-responsive self-assembled HG-type pectin nanomicelles for alleviating chronic alcoholic liver injury in mice

This study aimed to develop nanomicelles with redox-responsive properties using HG-type pectin (polygalacturonic acid) as a substrate to enhance the solubility of oleanolic acid (OA) and evaluate their potential application in the prevention of chronic alcoholic liver injury. Three amphiphilic conjugates, PA-OA, PA-S-OA, and PA-SS-OA (PA: polygalacturonic acid; S: 3,3'-thiodipropionic acid; SS: 3,3'-dithiobispropionic acid), were successfully synthesized by carbodiimide chemistry. The amphiphilic conjugates were physicochemically characterized and experimentally validated for efficacy in animal models. In aqueous solutions, these amphiphilic conjugates self-assembled to form nanomicelles with a particle size of approximately 430 nm and excellent stability. These nanomicelles exhibited superior water solubility compared with that of OA. In experiments simulating oxidizing and reducing environments to assess the degradation and OA release, PA-SS-OA exhibited superior redox responsiveness and achieved an efficient controlled release of OA. Erythrocyte hemolysis and cytotoxicity experiments demonstrated the excellent biocompatibility and safety of the prepared nanomicelles. In animal experiments, PA-SS-OA effectively mitigated alcohol-induced chronic liver injury by robustly stimulating the Nrf2 antioxidant response pathway, demonstrating a superior protective capacity compared with that of OA. These findings indicate that PA-SS-OA improves the bioavailability of OA and has potential applications in preventing chronic alcoholic liver injury.