In depth study of the polydopamine coating of liposomes as a potential alternative to PEGylation for the stabilization of nanocarriers in biological fluids

PEGylation is currently the most widespread strategy for the stabilization of nanocarriers for biomedical applications. However, the recognized stealth properties of PEG collide with accelerated blood clearance phenomena and frequently induced side effects. In this work, polydopamine (PDA), a bioinspired polymer, is proposed and evaluated as an alternative to PEG for liposome coating and stabilization. The PDA polymerization conditions are optimized, and the PDA-coated vesicles (Lipo@PDA) are fully characterized from a physicochemical point of view. Protein Corona (PC) formed after vesicle incubation in Fetal Bovine Serum (FBS) is characterized, given that PC determines the behavior of nanocarriers in biological fluids. Proteomic analysis reveals high homology between the most abundant recovered proteins in the PC of Lipo@PDA and PEG-coated liposomes (Lipo@PEG). From a quantitative standpoint, no significant differences were highlighted between the two systems. As for the hemolytic response, it is possible to stay within the 5% red blood cell lysis safety threshold by modulating the concentration and thickness of the PDA shell. Cyto-biocompatibility of Lipo@PDA and Lipo@PEG vesicles towards human respiratory cells NCI-H441 is evaluated. Both kinds of liposomes show a similar behavior: cytotoxicity slightly increases with their concentration. However, biocompatible Lipo@PDA vesicles are obtainable at all tested concentrations by reducing the thickness of the PDA coating. Gathered data suggest that the PDA coating can give the liposomes the same behavior in FBS as the PEG coating, thus offering an opportunity to overcome the drawbacks associated with the use of PEG.