Gelatinized-Core and Chitosan-Coated Liposomes: A Stabilized Carrier for Glutathione Delivery

Glutathione (GSH) is a bioactive tripeptide with potent antioxidant activity, but its oral delivery is limited by gastrointestinal instability and low membrane permeability. This study developed a biopolymer-stabilized liposomal system by combining gelatin incorporation into the aqueous core with low-molecular-weight chitosan (CS) coating to improve GSH retention and delivery characteristics. Conventional liposomes (GSH/CL), gelatinized-core liposomes (GSH/GL), and CS-coated gelatinized-core liposomes (CS-GSH/GL) were prepared and comparatively evaluated. GSH/GL exhibited higher entrapment efficiency than GSH/CL, with further enhancement following CS coating. The CS-GSH/GL formulation with 1.6 mg/mL CS was selected as the optimal formulation based on its overall physicochemical properties. CS-GSH/GL also exhibited improved retention of thiol groups under oxidative and acidic conditions and maintained a stable dispersion under the tested pH conditions. Under simulated gastrointestinal conditions, CS-GSH/GL showed the lowest cumulative GSH release among the liposomal formulations, indicating improved retention of encapsulated GSH. In Caco-2 cells, the CS-coated gelatinized-core formulation showed the highest fluorescence intensity when rhodamine B, a fluorescent model compound, was used. These findings indicate that the combined core gelatinization and CS coating improved the physicochemical stability and GSH retention of liposomes, while enhancing the cellular association of the rhodamine B-loaded liposomal delivery system. Overall, these in vitro findings support the potential of the formulation for GSH protection and retention, although further in vivo studies are needed to evaluate its bioavailability and safety.