Molecular dynamics simulation of PEGylated bilayer interacting with salt ions: a model of the liposome surface in the bloodstream.

PEGylation is an effective mechanism to prolong the bloodstream lifetime, and thus efficacy, of drug delivery liposomes. The mechanism through which poly(ethylene glycol) (PEG) increases bloodstream lifetime is, however, not completely understood. The interaction with salt ions found in the bloodstream is known to play a role in this. We have used all-atom molecular dynamics simulation to study the effect of PEGylated lipid density, salt concentration, and the interaction with KCl and CaCl(2) salts in addition to NaCl. Increasing the PEGylated lipid concentration in the formulation from 1:18 to 1:9 molar density decreased the extent to which the Cl(-) ions penetrated the PEG layer, thus causing the PEG layer to become effectively positively charged. The interaction of the PEG with the K(+) ions was weaker than for the Na(+) ions, and nonexistent for the Ca(2+) ions. This work expands on our previous work where we studied the gel and liquid crystalline membranes in physiological salt concentration. Our results provide both an explanation for the experimental observation that PEGylation inhibits calcium-induced liposome fusion and further insight into the mechanisms through which PEG may inhibit uptake of the liposome by the reticuloendothilial system (RES).