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

Abstract

Despite the well-known advantages of lipid vesicles fordrug andgene delivery, structural instability limits their practical applicationsand requires strictly regulated conditions for transport and storage.Chemical crosslinking and in situ polymerizationhave been suggested to increase the membrane rigidity and dispersionstability of lipid vesicles. However, such chemically modified lipidssacrifice the dynamic nature of lipid vesicles and obfuscate their in vivo metabolic fates. Here, we present highly robustmultilamellar lipid vesicles through the self-assembly of preformed,cationic large unilamellar vesicles (LUVs) with hydrolyzed collagenpeptides (HCPs). The cationic LUVs undergo vesicle-to-vesicle attachmentand structural reorganization through polyionic complexation withHCPs, resulting in the formation of multilamellar collagen-lipid vesicles(MCLVs). The resulting MCLVs exhibit excellent structural stabilityagainst variations in pH and ionic strength and the addition of surfactants.Particularly, the MCLVs maintain their structural stability againstrepeated freeze-thaw stresses, proving the unprecedented stabilizationeffect of biological macromolecules on lipid lamellar structures.This work provides a practically attractive technique for the simpleand quick fabrication of structurally robust lipid nanovesicles withoutcovalent crosslinkers, organic solvents, and specialized instruments.