RBCs-Derived Carriers for Targeted Delivery of Hepatoprotector Ademetionine to the Liver

Abstract

Background: Ademetionine is a highly polar and potent molecule used in various therapeutic applications, including liver diseases, depression, and other neurodegenerative disorders. However, its clinical application is limited due to its poor bioavailability and rapid clearance, with a half-life of about 1.5 hours, which is insufficient for sustained therapeutic effects. Aim: The aim of this research is to develop erythrocyte membrane-based transport containers for the targeted delivery of Ademetionine, with the goal of prolonging its accumulation in tissues Method: A hypo-osmotic hemolysis technique was implemented to obtain Ademetionine encapsulated erythrocytes. Quantification of total and unbound Ademetionine in the erythrocyte container was carried out using validated high-performance liquid chromatography (HPLC). Also, equilibrium dialysis techniques were used to assess the association and dissociation constants of Ademetionine within the carriers. Results: In vitro release studies demonstrated a biphasic release profile, with an initial burst phase peaking at 15 minutes (17.02 mg/ml ± 0.21), attributed to surface-adsorbed drug, followed by sustained release maintaining concentrations of 5–8 mg/ml over three hours, with complete depletion by 24 hours. These findings suggest that RBC-derived carriers are capable of providing controlled ademetionine delivery, supporting their potential as a hepatotropic platform for the management of liver dysfunction. Conclusion: Our findings indicate that the Erythrocyte transport container hold great potential to become a valuable drug-delivery platform of Ademetionine for the treatment of various diseases such as liver diseases. Key words: Ademetionine; drug delivery; erythrocyte transport container; equilibrium dialysis; hypo-osmotic hemolysis; poor bioavailability.