In this study, layer-by-layer self-assembled liposomes were prepared with different mixing ratios (3:7, 1:1, and 7:3) of sodium alginate (SA) and chitosan (CS), and the morphology, structure, and physicochemical properties of liposomes after layer-by-layer coating were investigated. After coating the liposomes with SA-CS layer-by-layer (S–C-L), the particle size of liposomes increased from 244.50 to 423.33 nm, the potential changed from negative to positive to 21.20 mV, and the PDI was only 0.393. In the S–C-L 7:3 formulation, the liposomes were uniformly distributed and spherical in size with a clear fingerprint structure. In addition, S–C-L reduced the number of hydrophobic regions within the molecule, allowing the phospholipid molecules to bind tightly into stacks, thus making the liposomes more stable. The S–C-L 7:3 formulation effectively improved the tolerance of liposomes to strong acids and bases, high-salt environments, and UV exposure, and maintained a constant particle size of 400 nm after 28 days of storage. The findings of this study might contribute to the development of polysaccharide layer-by-layer modification of liposomes for a more stable liposomal transport system.
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