Functionalized chitosan coatings via amino acid grafting: A strategy to improve liposomal stability and bioactivity

Chitosan (CS) coatings can improve the stability and bioactivity of liposomes; however, native CS suffers from poor solubility, high viscosity, and pH-dependent charge, restricting its practical use. In this study, amino acid-grafted CS (AA-g-CS) derivatives, such as l-lysine (Lys-g-CS), L-arginine (Arg-g-CS), and L-asparagine (Asn-g-CS), were synthesized and evaluated as liposomal coatings to enhance colloidal stability and biological performance. Coating liposomes at a 5:1 lipid-to-polymer ratio was found to be optimal, resulting in uniform nanocarriers (110.7-153.8 nm) for all derivatives. Compared to unmodified CS, Arg-g-CS and Asn-g-CS coatings significantly improved liposomal stability. They remained relatively stable in phosphate-buffered saline (PBS) and sodium bicarbonate and maintained their structural integrity over 60 days of storage at 4 °C, outperforming other formulations. All coatings controlled the release of curcumin from liposomes within 24 h. Additionally, amino acid modification allowed tunable antibacterial effects for both the polymers and the liposomes. The coated liposomes exhibited good biocompatibility in B16-F10 cells (cell viability >75 % at concentrations up to 125 μg/mL), and cellular uptake was efficient across all coatings within 120 min, with Arg-g-CS-coated liposomes showing the highest internalization. These findings highlight AA-g-CS as a versatile strategy to overcome the physicochemical limitations of native CS, enabling the design of stable, bioactive, and biocompatible liposomal delivery systems for certain biomedical applications.