Attenuation of Liver Injury via Bicyclol–Bovine Serum Albumin Nanopreparation using a Green Synthetic Approach

Bicyclol (BIC) is a traditional antihepatitis drug that is used to treat chronic hepatitis B infections by improving liver function and reducing transaminase levels. Because the extensive use of BIC for treating liver injury is limited by its poor bioavailability, the course of treatment with oral BIC lasted for >6 months. This study aimed to develop a nano-BIC injection to improve its bioavailability and anti-hepatitis efficacy. We used a green synthetic approach to prepare BIC-bovine serum albumin (BSA) nanoparticles (BIC-NPs). Moderate protein denaturation is required to release free thiol groups in the intramolecular reactions of BSA, which may form an intermolecular disulfide network to stabilize the BIC–BSA nanoassembly. Our results showed that the administration of BIC-NPs in rats resulted in a 2.42-fold increase in drug concentration in plasma. Further, nano-BIC injection showed high bioavailability and rapidly achieved therapeutic concentrations. BIC can restore mitochondrial function by scavenging reactive oxygen species. Moreover, we observed that 70 nm NPs can accumulate in the liver, and the nano-BIC injection protected mice from methotrexate-induced liver injury. This study provides an improved strategy for developing a liver-protecting agent to meet various clinical needs of patients.