Highly Robust Multilamellar Lipid Vesicles Generated through Intervesicular Self-assembly Mediated by Hydrolyzed Collagen Peptides

Despite the advantages of lipid vesicles for drug and gene delivery, structural instability limits their practical applications and requires strictly regulated conditions for transport and storage. Chemical crosslinking and in situ polymerization have been suggested to increase the membrane rigidity and dispersion stability of lipid vesicles. However, such chemically modified lipids sacrifice the dynamic nature of lipid vesicles and obfuscate their in vivo metabolic fates. Here we present highly robust multilamellar lipid vesicles through the self-assembly of pre-formed, cationic large unilamellar vesicles (LUVs) with hydrolyzed collagen peptides (HCPs). The cationic LUVs undergo vesicle-to-vesicle attachment and structural reorganization through polyionic complexation with HCPs, resulting in the formation of multilamellar collagen-lipid vesicles (MCLVs). The resulting MCLVs exhibit excellent structural stability against variations in pH and ionic strength and the addition of surfactants. Particularly, the MCLVs maintain their structural stability against repeated freeze-thaw stresses, proving the excellent stabilization effect of HCPs on lipid lamellar structures. This work provides a practically attractive technique for the simple and quick fabrication of structurally robust lipid nanovesicles without covalent crosslinkers, organic solvents, and specialized instruments.