Effects of PEGylation on Liposome Degradation by a Model Phospholipase

Polyethylene glycol (PEG) has been conjugated to phospholipids to form liposomes with longer blood circulation time, since PEG brushes prevent non-specific protein adsorption and help particles escape phagocytosis. Although PEG provides steric repulsions, it also affects lipid packing and liposome stability. We report here liposomes hydrolysis catalyzed by secreted phospholipase A2 (sPLA2), with an emphasis on revealing the contradictory effects of PEG. The kinetics of liposome hydrolysis were studied by dynamic light scattering. We measured the hydrolysis lag times of liposomes by monitoring the changes in size after mixing with different concentrations of sPLA2. The results followed two exponential functions, defining regimes of degradation kinetics. The effects of PEGylation on the packing of the phospholipid monolayers were studied using X-ray reflectivity and grazing incidence diffraction. The packing of phospholipid monolayers was just slightly disturbed with the inclusion of 5-10\% PEGylation (PEG Mw 2000-5000). However, sPLA2 induced hydrolysis of liposomes with higher degrees of PEGylation appeared to be attenuated. In sum, the effects of PEGylation on the protection of lipid assemblies overcomes their disturbance on the lipid packing in the range of our experiments.